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研究生:張凱維
研究生(外文):Kai-Wei Chang
論文名稱:以系統生物學方法探討表觀基因調控在雞胚胎組織發育命運決定上的作用
論文名稱(外文):Using Systems Biology Approaches to Study Epigenetic Regulation on Chicken Embryonic Cell Fate Decision
指導教授:林劭品
指導教授(外文):Shau-Ping Lin
口試委員:劉逸軒林詩舜黃憲松林頌然陳倩瑜林恩仲Antonin Morillon
口試委員(外文):I-Hsuan LiuShih-Shun LinHsien-Sung HuangSung-Jan LinChien-Yu ChenEn-Chung LinAntonin Morillon
口試日期:2017-04-11
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:基因體與系統生物學學位學程
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:141
中文關鍵詞:發育胚胎皮膚生殖細胞餘弦相似度分析染色質免疫沉澱法生物資訊piRNA轉錄
外文關鍵詞:ChickenDevelopmentEmbryoSkinGerm CellCosine SimilarityChromatin IPBioinformaticspiRNATranscription
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表觀基因控制機制(epigenetic regulation)可解釋為在基因體上控制各基因位點開啟或關閉的機制。因此,表觀基因特徵往往決定了基因轉錄表現及細胞身份。表觀基因體亦具有遺傳特性。因此在細胞命運決定過程中,表觀基因不但參與分化進程,並能保存分化「記憶」並依此進行後繼調控。表觀基因控制機制概括涵蓋DNA甲基化修飾(DNA methylation)、組蛋白修飾(histone modification)、功能性非編碼RNA(functional non-coding RNA)等多層次分子控制機制。因此,表觀基因控制機制如何系統性影響細胞命運決定,變成為相當值得研究的課題。我在這篇論文中提出兩個研究主題,主旨皆在以系統生物學方法,分析探討在不同發育位置和發育時間上,表觀基因調控對細胞命運決定的影響。本論文使用雞為模式生物。
在第一個研究主題中(第二章),我們知道雞的背部羽毛生成皮膚和蹠部鱗片生成皮膚構型上有顯著差異,但文獻指出未分化的早期胚胎表皮可在一段短暫期間內,依照所接觸的真皮層決定分化進程。我認為表皮的表觀基因控制機制,尤其在增強子(enhancer)調控方面,可能反應真皮層訊號,從而參與此命運決定現象。在合作夥伴的協助下,我們以無偏見餘弦相似性(cosine similarity)分析20組涵蓋分化、未分化、表皮、真皮、背部、蹠部的微陣列基因表現資料,並發現鈣離子訊號網路基因可能系統性參與並影響表皮命運決定的進程。我更進一步克服未分化表皮細胞不足的弊端,以微量細胞進行染色質免疫沉澱定序分析(ChIP-seq),取得增強子調控相關的組蛋白修飾位點,並藉此得知早期未分化細胞在鈣離子訊號網路基因的增強子活動上已有的不同,並可能依此引導表皮命運決定的進程。
在第二個研究主題中(第三章),已知PIWI/piRNA調控路徑在抑制跳躍子(transposable elements)機制中扮演重要角色。但是目前學界對piRNA的前驅體—piRNA基因簇(piRNA cluster)的轉錄調控所知甚少。在已知piRNA基因簇和蛋白表現基因同是經由第二型RNA聚合酶(Pol II)轉錄的情況下,我進一步假設一些與Pol II合作的轉錄因子也可能參與piRNA基因簇的轉錄調控。我與研究同儕合作設計並優化判定piRNA序列的生物資訊分析平台,取得雞胚盤細胞piRNA、第11天及第14天的雄雞胚胎生殖腺、與雄雞睪丸的piRNA資料。我發現雞性腺piRNA會循發育階段,逐漸由跳躍子相關的piRNA序列轉為基因間區段(intergenic region)相關的piRNA序列。我在進一步分析piRNA基因簇表現時,發現階段性表現的piRNA基因簇通常具有階段性表現的轉錄因子的作用位點,顯示兩者的相關性。在延伸研究時我意外發現,在第11天及第14天的雄雞胚胎生殖腺高量表現的piRNA可能參與抑制神經發育相關基因的轉錄。這個發現暗示piRNA可能參與抑制生殖細胞往非生殖細胞方向分化。
對於本論文探討的兩個主題中,我實踐運用系統生物學的分析理論及方法,綜合生物資訊、生物統計、及細胞與分子生物學操作,找出兩種表觀基因在細胞命運決定時的調控機制,並對表觀基因調控在發育上的影響產生更深一層的認知。
Epigenetic regulation describes multiple layers of signatures that are involved in governing the accessibilities of genomic regions. These signatures hence configure the gene expression patterns that define cell identity as well as drive cell fate decision. Additionally, epigenomes are mitotically heritable that serve to “remember” the differentiation progress and prepare for further modulation. Nevertheless, the relationships between epigenetic regulation and cell fate decision involved in many faces that have yet been understood. This thesis is comprised by two separate hypothesis, but all pointing to the understanding of spatiotemporal regulation of epigenome that lead to cell fate commitment. Here, chicken is used as the model organism in this thesis.
In my first project (chapter 2), given feather forming dorsal skin and scale forming metatarsal skin display dramatically different characteristics, but was found having interchangeable fate in early embryonic skin epithelium. How primal skins can develop into distinct features is becoming of interest. I hypothesize that region specific differentiation of skin epithelium cells is, at least partially, regulated by specific regulatory pathways and histone modification machineries triggered by mesenchymal signaling. In collaboration efforts, we applied unbiased cosine similarity analysis on 20 microarray expression profiles of undifferentiated and differentiated epithelium and mesenchymes for dorsal and metatarsal skin regions, and found genes involved calcium signaling pathway are regulated spatiotemporally regulated in association with each skin part in question. For investigation of cis enhancer activities associated with these genes, I successfully applied ChIP-seq for small number of cells and solved the limitation of low cell yields from undifferentiated skins. The result identified the enhancer signatures on calcium signaling pathway subunits are correlated with their gene expression, and in turn favor the fate decision toward scale-forming skins.
In the next project (chapter 3), I was focused in PIWI/piRNA pathway which is an important epigenetic regulatory machinery in silencing transposable elements (TEs) during germ cell development. Nevertheless, transcriptional regulation of piRNA cluster, which crucially shape piRNA profiles, was scarcely reported, particularly for piRNA clusters localized on intergenic regions. PiRNA clusters are transcribed by Pol II as for typical genes. I hypothesize some specific transcriptional factors may be involved in stage-dependent piRNA cluster regulations. In collaboration with colleagues, we designed and optimized bioinformatics pipeline for piRNA candidate filtering. I found transition of piRNA profiles from TE associated piRNAs to intergenic region orientated piRNAs along development from blastodermal cell to adult, which the result imply stage dependent regulation. Based on transcription factor binding site analysis, I identified some transcription factors may be involved in the developmental stage-dependent expression of piRNA clusters. The expression analysis further showed most of these transcription factors are also regulated in stage-dependent manner. In extension of this study, I found the stage-dependently regulated piRNAs in E11 and E14 male gonads are preferentially targeting to genes involved in neurogenesis. This finding imply expression repression, and therefore likely suppress cell fate development toward neuron lineages.
In summary, I applied systems biology perspective to both research arms, and identified two epigenetic regulatory features that likely contribute to epigenomic landscape for cell fate decision. These discoveries contribute to the further understanding of how epigenomic regulation may be involved for cell fate decision.
TABLE OF CONTENTS
Acknowledgement ii
口試委員會審定書 iii
ABSTRACT iv
中文摘要 vi
Publications Arising from This Thesis viii
Publications viii
Manuscripts ix
Table of Contents x
List of Figures xv
List of Tables xviii
CHAPTER 1 Overview 19
1.1 Introduction 20
1.2 Epigenetics 21
1.3 DNA methylation 22
1.3.1 Addition and Maintenance of DNA Methylation 22
1.3.2 DNA demethylation 23
1.4 Histone modification 23
1.4.1 Histone Signatures associated with Transcriptional Regulation 24
1.5 Functional non-coding RNA 25
1.5.1 Dicer-dependent small RNAs 25
1.5.2 PIWI-interacting RNAs 26
1.5.3 Long non-coding RNAs 27
1.6 Epigenetic Memory and Reprogramming 27
1.7 Summary 28
1.8 References 29
CHAPTER 2 Emergence of Differentially Regulated Pathways Associated with the Development of Regional Specificity in Chicken Skin 36
2.1 Abstract 37
2.2 Background 38
2.3 Methods 41
2.3.1 Animal ethics statement 41
2.3.2 Microarray Profiles 41
2.3.3 Cosine Similarity Analysis 42
2.3.3-1 Seed (candidate genes) selection 43
2.3.3-2 Identification of genes co-regulated or reciprocally regulated with seeds 44
2.3.3-3 Identification of key regulators by exploratory data analysis 44
2.3.4 Sample Collection for Gene Expression and Chromatin Analysis 44
2.3.5 RNA Purification 45
2.3.6 Reverse Transcription-qPCR (RT-qPCR) 45
2.3.7 In Situ Hybridization 46
2.3.8 Chromatin Immunoprecipitation (ChIP)-next generation sequencing (ChIP-seq) and qPCR 46
2.4 Results and Discussion 47
2.4.1 Identification of Differentially Regulated and Co-regulated Pathways in Different Skin Regions Using Cosine Similarity Analysis 47
2.4.2 The calcium signaling pathway is differentially expressed in developing feather and scale regions 52
2.4.3 Potential enhancers for calcium channel genes are identified based on the specific combination of histone modifications 58
2.5 Conclusion 60
2.6 List of abbreviations 67
2.7 References 68
2.8 Appendix 76
CHAPTER 3 Developmental Stage-Dependent Regulation of piRNA Clusters in Chicken and Their Potential Roles in Cell Fate Decision toward Germ Cell Development 79
3.1 Abstract 80
3.2 Introduction 80
3.3 Material and Method 83
3.3.1 Bioinformatics filtering for piRNA candidates 83
3.3.2 Strand-specific RNA-seq analysis 85
3.3.3 piRNA cluster analysis 85
3.3.4 Transcription factor binding site enrichment analysis 86
3.3.5 Animals and tissue sample collection 87
3.3.6 PGC isolation and in vitro culture 87
3.3.7 Germ cell purification 87
3.3.8 Immunocytochemistry 88
3.3.9 Total RNA isolation and Reverse Transcription Real-time PCR (RT-qPCR) 88
3.4 Result 89
3.4.1 piRNA components and composition varied according to developmental stages 89
3.4.2 piRNA Cluster analysis identified stage-dependent piRNA cluster expression patterns 93
3.4.3 Transcription factors likely contribute to the regulation of stage-enriched piRNA clusters 96
3.4.4 piRNAs from embryonic gonadal piRNA clusters may be involved in repressing genes involve in neurogenesis 100
3.5 Discussion 104
3.5.1 Comparison of the piRNA features along germ cell developmental timelines between chicken and mouse 104
3.5.2 Ping-pong cycle analysis may imply changes in ping-pong cycle machineries in different developmental stages 105
3.5.3 Stage-dependently expressed transcription factors may be involved in stage-enriched piRNA clusters 106
3.5.4 Stage-dependent transcription factors may be involved in the transcription of stage-enriched piRNA clusters 106
3.5.5 PiRNAs originated from stage-enriched piRNA clusters may be involved in fine tuning germ line developmental pathway 107
3.6 Summary 109
3.7. List of abbreviations 109
3.8 Reference 110
3.9 Appendix 122
CHAPTER 4 Discussions and perspectives 127
4.1 Unbiased Analysis towards a System 128
4.2 A Shift of Focus from Skin Development to Germ Cell Development 129
4.3 Advantages and Limitation 130
4.3.1 Chicken is an interesting model for comparative study with mammal (mouse) 130
4.3.2 Knowledge bias using public available databases 131
4.4 Potential Follow-ups 132
4.4.1 Follow-up experimental design for investigating roles of calcium signaling in embryonic skin epithelium fate decision 132
4.4.2 Analysis on the correlations between stage-enriched piRNA clusters and their potentially associated transcription factors 133
4.5 Additional discoveries from this study 134
4.5.1 Additional discovery and discussions based on the calcium signaling associated differentiation settings for feather/scale skin development (Chapter 2) 134
4.5.2 Additional discovery and discussions based on stage-dependently regulate piRNA clusters (Chapter 3) 136
4.6 Summary 138
4.7 References 139


LIST OF FIGURES
Chapter 1
Figure 1. 1 Epigenomic settings pave the pathways for cell fate decision. 20
Chapter 2
Figure 2. 1 Cosine similarity analysis methodology for determining co-differentially regulated genes in the feather/scale region. 43
Figure 2. 2 Developmental progress of feather skin and scale skin. 48
Figure 2. 3 GSEA coupled with interaction pathway analysis on embryonic development GO terms. 49
Figure 2. 4 Differentially regulated genes involved in calcium signaling pathways. 53
Figure 2. 5 RT-qPCR validation of the differentially regulated calcium channel genes at the epithelium 55
Figure 2. 6 RT-qPCR for other calcium channel subunit genes. 56
Figure 2. 7 Whole mount in situ hybridization of CACNA1D and CACNA2D1 in E7 feather forming and E9 scale forming regions. 57
Figure 2. 8 ChIP-qPCR of the potential enhancer regions that may be associated with CACNA1D gene activities. 61
Figure 2. 9 ChIP-qPCR of the potential enhancer regions that may be associated with CACNA1H gene activities. 62
Figure 2. 10 ChIP-qPCR of the potential enhancer regions that may be associated with CACNA2D1 gene activities. 63
Figure 2. 11 ChIP-qPCR of the potential enhancer regions that may be associated with CACNA1C gene activities. 64
Figure 2. 12 ChIP-qPCR of the potential enhancer regions that may be associated with CACNA1G gene activities. 65
Figure 2. 13 ChIP-qPCR of the potential enhancer regions that may be associated with CACNA2D3 gene activities. 66
Chapter 3
Figure 3. 1 Bioinformatics analysis for identifying candidate piRNAs. 84
Figure 3. 2 Schematic presentation of merging piRNAs from multiple stages. 86
Figure 3. 3 Features of chicken piRNA Candidates 90
Figure 3. 4 Analysis for ping-pong cycle signature. 91
Figure 3. 5 Genomic association for piRNA candidates of stage-enriched sizes. 92
Figure 3. 6 piRNA cluster analysis and classification showing stage-dependent expression profiles of germ cell associated piRNA clusters. 94
Figure 3. 7 Analysis of germ cell properties to validate germ cell enrichment efficiency. 97
Figure 3. 8 Identification of transcription factors likely involved in stage dependent piRNA cluster regulation. 98
Figure 3. 9 Application of RT-qPCR to determine the expressions of picaTFs in circulating PGC (cPGC), E6 gonadal PGC (gPGC), and enriched germ cell populations from E11 gonad (E11G_Germ) and E14 gonad (E14G_Germ). 99
Figure 3. 10 Schematic representation of the regulation over piRNA clusters involve in the regulation over germ cell development. 100
Figure 3. 11 Target analysis for stage-enriched, cluster-able piRNAs. 101
Figure 3. 12 Ontology analysis for genes targeted by stage-enriched piRNAs, 102
Figure 3. 13 Application of RT-qPCR to evaluate expression pattern of genes involved in neurogenesis and targeted by stage-enriched piRNAs 103
Chapter 4
Figure 4. 1 Ordinary differential equations (ODE) used for dynamic modeling to exam negative crosstalk behaviors by WNT/β-catenin and WNT/Ca2+. 135
Figure 4. 2 Example of some piRNA clusters that may be conserved across high vertebrates but may be stage-dependently regulated. 136
Figure 4. 3 Example of varied piRNA targeting strength to ERVL family members in different germline developmental stages. 137


LIST OF TABLES
Chapter 2
Table 2. 1 Candidate microarray probes from the cosine similarity analysis. 50
Table 2. 2 Top 5 significant KEGG pathways identified based on the differentially regulated genes and co-regulated genes from cosine similarity analysis. 51

Supplementary Table 2. 1 Primer sets for RT-qPCR. 76
Supplementary Table 2. 2 Primer sets for ChIP-qPCR. 77
Supplementary Table 2. 3 KEGG pathways identified based on the differentially regulate genes and co-regulated genes from cosine similarity analysis. 78

Chapter 3
Table 3. 1 Cluster-able piRNAs before and after piRNA cluster merge 94
Table 3. 2 PiRNA clusters that embody TE sequences 95
Table 3. 3 TE associated Cluster-able piRNAs, by developmental stages 96

Supplementary Table 3 1 RT-qPCR primer sets 122
Chapter 1
1.Waddington CH: The strategy of the genes; a discussion of some aspects of theoretical biology. London,: Allen [and] Unwin; 1957.
2.Deal RB, Henikoff S: A simple method for gene expression and chromatin profiling of individual cell types within a tissue. Developmental cell 2010, 18(6):1030-1040.
3.Mo A, Mukamel EA, Davis FP, Luo C, Henry GL, Picard S, Urich MA, Nery JR, Sejnowski TJ, Lister R et al: Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. Neuron 2015, 86(6):1369-1384.
4.Liu Y, Giannopoulou EG, Wen D, Falciatori I, Elemento O, Allis CD, Rafii S, Seandel M: Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells. Nat Commun 2016, 7:11275.
5.Moris N, Pina C, Arias AM: Transition states and cell fate decisions in epigenetic landscapes. Nature reviews Genetics 2016, 17(11):693-703.
6.Dodge JE, Ramsahoye BH, Wo ZG, Okano M, Li E: De novo methylation of MMLV provirus in embryonic stem cells: CpG versus non-CpG methylation. Gene 2002, 289(1-2):41-48.
7.Haines TR, Rodenhiser DI, Ainsworth PJ: Allele-specific non-CpG methylation of the Nf1 gene during early mouse development. Developmental biology 2001, 240(2):585-598.
8.Suzuki MM, Bird A: DNA methylation landscapes: provocative insights from epigenomics. Nature reviews Genetics 2008, 9(6):465-476.
9.Deaton AM, Bird A: CpG islands and the regulation of transcription. Genes & development 2011, 25(10):1010-1022.
10.Illingworth RS, Bird AP: CpG islands--''a rough guide''. FEBS Lett 2009, 583(11):1713-1720.
11.Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X: Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 2007, 449(7159):248-251.
12.Bestor TH, Ingram VM: Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc Natl Acad Sci U S A 1983, 80(18):5559-5563.
13.Schrader A, Gross T, Thalhammer V, Langst G: Characterization of Dnmt1 Binding and DNA Methylation on Nucleosomes and Nucleosomal Arrays. PLoS One 2015, 10(10):e0140076.
14.Chen T, Hevi S, Gay F, Tsujimoto N, He T, Zhang B, Ueda Y, Li E: Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nature genetics 2007, 39(3):391-396.
15.He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L et al: Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 2011, 333(6047):1303-1307.
16.Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C: Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat Chem Biol 2012, 8(4):328-330.
17.Kohli RM, Zhang Y: TET enzymes, TDG and the dynamics of DNA demethylation. Nature 2013, 502(7472):472-479.
18.Luger K: Structure and dynamic behavior of nucleosomes. Curr Opin Genet Dev 2003, 13(2):127-135.
19.Allis CD, Jenuwein T: The molecular hallmarks of epigenetic control. Nature reviews Genetics 2016, 17(8):487-500.
20.Cann KL, Dellaire G: Heterochromatin and the DNA damage response: the need to relax. Biochem Cell Biol 2011, 89(1):45-60.
21.Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA et al: Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nature genetics 2007, 39(3):311-318.
22.Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K: High-resolution profiling of histone methylations in the human genome. Cell 2007, 129(4):823-837.
23.Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA: A chromatin landmark and transcription initiation at most promoters in human cells. Cell 2007, 130(1):77-88.
24.Hon GC, Hawkins RD, Ren B: Predictive chromatin signatures in the mammalian genome. Hum Mol Genet 2009, 18(R2):R195-201.
25.Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA et al: Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 2010, 107(50):21931-21936.
26.Becker JS, Nicetto D, Zaret KS: H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes. Trends in genetics : TIG 2016, 32(1):29-41.
27.Shlyueva D, Stampfel G, Stark A: Transcriptional enhancers: from properties to genome-wide predictions. Nature reviews Genetics 2014, 15(4):272-286.
28.Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J: A unique chromatin signature uncovers early developmental enhancers in humans. Nature 2011, 470(7333):279-283.
29.Jamieson K, Wiles ET, McNaught KJ, Sidoli S, Leggett N, Shao Y, Garcia BA, Selker EU: Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin. Genome research 2016, 26(1):97-107.
30.Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP et al: Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 2007, 448(7153):553-560.
31.Hutvagner G, Simard MJ: Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol 2008, 9(1):22-32.
32.Filipowicz W, Bhattacharyya SN, Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature reviews Genetics 2008, 9(2):102-114.
33.Ji L, Chen X: Regulation of small RNA stability: methylation and beyond. Cell research 2012, 22(4):624-636.
34.Kirino Y, Mourelatos Z: Mouse Piwi-interacting RNAs are 2''-O-methylated at their 3'' termini. Nat Struct Mol Biol 2007, 14(4):347-348.
35.Pezic D, Manakov SA, Sachidanandam R, Aravin AA: piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes & development 2014, 28(13):1410-1428.
36.Gou LT, Dai P, Yang JH, Xue Y, Hu YP, Zhou Y, Kang JY, Wang X, Li H, Hua MM et al: Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell research 2014, 24(6):680-700.
37.Zhang P, Kang JY, Gou LT, Wang J, Xue Y, Skogerboe G, Dai P, Huang DW, Chen R, Fu XD et al: MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell research 2015, 25(2):193-207.
38.Yin QF, Yang L, Zhang Y, Xiang JF, Wu YW, Carmichael GG, Chen LL: Long noncoding RNAs with snoRNA ends. Mol Cell 2012, 48(2):219-230.
39.Hellwig S, Bass BL: A starvation-induced noncoding RNA modulates expression of Dicer-regulated genes. Proc Natl Acad Sci U S A 2008, 105(35):12897-12902.
40.Du Z, Sun T, Hacisuleyman E, Fei T, Wang X, Brown M, Rinn JL, Lee MG, Chen Y, Kantoff PW et al: Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer. Nat Commun 2016, 7:10982.
41.Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL, De S, Huarte M, Zhan M, Becker KG, Gorospe M: LincRNA-p21 suppresses target mRNA translation. Mol Cell 2012, 47(4):648-655.
42.Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T, Luco RF: A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nat Struct Mol Biol 2015, 22(5):370-376.
43.Wutz A, Gribnau J: X inactivation Xplained. Curr Opin Genet Dev 2007, 17(5):387-393.
44.Wutz A: Xist function: bridging chromatin and stem cells. Trends in genetics : TIG 2007, 23(9):457-464.
45.Pereira JD, Sansom SN, Smith J, Dobenecker MW, Tarakhovsky A, Livesey FJ: Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proc Natl Acad Sci U S A 2010, 107(36):15957-15962.
46.Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY: Long noncoding RNA as modular scaffold of histone modification complexes. Science 2010, 329(5992):689-693.
47.Law JA, Jacobsen SE: Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature reviews Genetics 2010, 11(3):204-220.
48.Margueron R, Reinberg D: Chromatin structure and the inheritance of epigenetic information. Nature reviews Genetics 2010, 11(4):285-296.
49.Messerschmidt DM, Knowles BB, Solter D: DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes & development 2014, 28(8):812-828.
50.Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, Popp C, Thienpont B, Dean W, Reik W: The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 2012, 48(6):849-862.
51.Hajkova P: Epigenetic reprogramming in the germline: towards the ground state of the epigenome. Philosophical transactions of the Royal Society of London Series B, Biological sciences 2011, 366(1575):2266-2273.

Chapter 2
1.Prin F, Dhouailly D: How and when the regional competence of chick epidermis is established: feathers vs. scutate and reticulate scales, a problem en route to a solution. Int J Dev Biol 2004, 48(2-3):137-148.
2.Stettenheim PR: The Integumentary Morphology of Modern Birds—An Overview. American Zoologist 2000, 40(4):461-477.
3.Chang CH, Jiang TX, Lin CM, Burrus LW, Chuong CM, Widelitz R: Distinct Wnt members regulate the hierarchical morphogenesis of skin regions (spinal tract) and individual feathers. Mech Dev 2004, 121(2):157-171.
4.Yue Z, Jiang TX, Widelitz RB, Chuong CM: Mapping stem cell activities in the feather follicle. Nature 2005, 438(7070):1026-1029.
5.Yue Z, Jiang TX, Widelitz RB, Chuong CM: Wnt3a gradient converts radial to bilateral feather symmetry via topological arrangement of epithelia. Proc Natl Acad Sci U S A 2006, 103(4):951-955.
6.Jiang TX, Widelitz RB, Shen WM, Will P, Wu DY, Lin CM, Jung HS, Chuong CM: Integument pattern formation involves genetic and epigenetic controls: feather arrays simulated by digital hormone models. Int J Dev Biol 2004, 48(2-3):117-135.
7.Mandler M, Neubuser A: FGF signaling is required for initiation of feather placode development. Development 2004, 131(14):3333-3343.
8.Noramly S, Morgan BA: BMPs mediate lateral inhibition at successive stages in feather tract development. Development 1998, 125(19):3775-3787.
9.McKinnell IW, Turmaine M, Patel K: Sonic Hedgehog functions by localizing the region of proliferation in early developing feather buds. Developmental biology 2004, 272(1):76-88.
10.Noramly S, Freeman A, Morgan BA: beta-catenin signaling can initiate feather bud development. Development 1999, 126(16):3509-3521.
11.Chodankar R, Chang CH, Yue Z, Jiang TX, Suksaweang S, Burrus L, Chuong CM, Widelitz R: Shift of localized growth zones contributes to skin appendage morphogenesis: role of the Wnt/beta-catenin pathway. The Journal of investigative dermatology 2003, 120(1):20-26.
12.Lin CM, Jiang TX, Widelitz RB, Chuong CM: Molecular signaling in feather morphogenesis. Current opinion in cell biology 2006, 18(6):730-741.
13.Harris MP, Fallon JF, Prum RO: Shh-Bmp2 signaling module and the evolutionary origin and diversification of feathers. The Journal of experimental zoology 2002, 294(2):160-176.
14.Dhouailly D, Hardy MH, Sengel P: Formation of feathers on chick foot scales: a stage-dependent morphogenetic response to retinoic acid. Journal of embryology and experimental morphology 1980, 58:63-78.
15.Crowe R, Niswander L: Disruption of scale development by Delta-1 misexpression. Developmental biology 1998, 195(1):70-74.
16.Widelitz RB, Jiang TX, Lu J, Chuong CM: beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin. Developmental biology 2000, 219(1):98-114.
17.Zou H, Niswander L: Requirement for BMP signaling in interdigital apoptosis and scale formation. Science 1996, 272(5262):738-741.
18.Mou C, Pitel F, Gourichon D, Vignoles F, Tzika A, Tato P, Yu L, Burt DW, Bed''hom B, Tixier-Boichard M et al: Cryptic patterning of avian skin confers a developmental facility for loss of neck feathering. PLoS biology 2011, 9(3):e1001028.
19.Rawles ME: Tissue Interactions in Scale and Feather Development as Studied in Dermal-Epidermal Recombinations. Journal of embryology and experimental morphology 1963, 11:765-789.
20.Dhouailly D: Dermo-epidermal interactions between birds and mammals: differentiation of cutaneous appendages. Journal of embryology and experimental morphology 1973, 30(3):587-603.
21.Hughes MW, Wu P, Jiang TX, Lin SJ, Dong CY, Li A, Hsieh FJ, Widelitz RB, Chuong CM: In search of the Golden Fleece: unraveling principles of morphogenesis by studying the integrative biology of skin appendages. Integrative biology : quantitative biosciences from nano to macro 2011, 3(4):388-407.
22.R Core Team: R: A Language and Environment for Statistical Computing. In.: R Foundation for Statistical Computing; 2014.
23.Gautier L, Cope L, Bolstad BM, Irizarry RA: affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 2004, 20(3):307-315.
24.Frohlich H, Speer N, Poustka A, Beissbarth T: GOSim--an R-package for computation of information theoretic GO similarities between terms and gene products. BMC Bioinformatics 2007, 8:166.
25.Cheng J, Xie Q, Kumar V, Hurle M, Freudenberg JM, Yang L, Agarwal P: Evaluation of analytical methods for connectivity map data. Pacific Symposium on Biocomputing Pacific Symposium on Biocomputing 2013:5-16.
26.Sethi P, Alagiriswamy S: Association rule based similarity measures for the clustering of gene expression data. The open medical informatics journal 2010, 4:63-73.
27.Dzuida DM: Data mining for genomics and proteomics : analysis of gene and protein expression data. Hoboken, N.J.: Wiley; 2010.
28.Revelle W: psych: Procedures for Psychological, Psychometric, and Personality Research. In. Evanston, Illinois: Northwestern University; 2014.
29.Hamburger V, Hamilton HL: A series of normal stages in the development of the chick embryo. 1951. Developmental dynamics : an official publication of the American Association of Anatomists 1992, 195(4):231-272.
30.Jiang T-X, Stott S, Widelitz RB, Chuong C-M: Current methods in the study of avian skin appendages. In: Molecular Basis of Epithelial Appendage Morphogenesis. Edited by Chuong C-M, Austin TX: Landes Bioscience; 1998: 395-408.
31.Langmead B, Salzberg SL: Fast gapped-read alignment with Bowtie 2. Nature methods 2012, 9(4):357-359.
32.Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W et al: Model-based analysis of ChIP-Seq (MACS). Genome biology 2008, 9(9):R137.
33.Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES et al: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005, 102(43):15545-15550.
34.Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E et al: PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature genetics 2003, 34(3):267-273.
35.Ille F, Atanasoski S, Falk S, Ittner LM, Marki D, Buchmann-Moller S, Wurdak H, Suter U, Taketo MM, Sommer L: Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord. Developmental biology 2007, 304(1):394-408.
36.Katoh M: Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem cell reviews 2007, 3(1):30-38.
37.Parikh JR, Klinger B, Xia Y, Marto JA, Bluthgen N: Discovering causal signaling pathways through gene-expression patterns. Nucleic Acids Res 2010, 38(Web Server issue):W109-117.
38.Omori Y, Katoh K, Sato S, Muranishi Y, Chaya T, Onishi A, Minami T, Fujikado T, Furukawa T: Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina. PLoS One 2011, 6(5):e19685.
39.Glass K, Ott E, Losert W, Girvan M: Implications of functional similarity for gene regulatory interactions. Journal of the Royal Society, Interface / the Royal Society 2012, 9(72):1625-1636.
40.Fisher R: Frequency Distribution of the Values of the Correlation Coefficient in Samples from an Indefinitely Large Population. Biometrika 1915, 10(4).
41.Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C et al: STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013, 41(Database issue):D808-815.
42.Rivals I, Personnaz L, Taing L, Potier MC: Enrichment or depletion of a GO category within a class of genes: which test? Bioinformatics 2007, 23(4):401-407.
43.Jiang TX, Jung HS, Widelitz RB, Chuong CM: Self-organization of periodic patterns by dissociated feather mesenchymal cells and the regulation of size, number and spacing of primordia. Development 1999, 126(22):4997-5009.
44.Dhouailly D: Dermo-epidermal interactions during morphogenesis of cutaneous appendages in amniotes. Frontiers of Matrix Biology 1977, 4:86-121.
45.Hardy MH: The secret life of the hair follicle. Trends in genetics : TIG 1992, 8(2):55-61.
46.Chuong CM, Widelitz RB, Ting-Berreth S, Jiang TX: Early events during avian skin appendage regeneration: dependence on epithelial-mesenchymal interaction and order of molecular reappearance. The Journal of investigative dermatology 1996, 107(4):639-646.
47.Park HY, Russakovsky V, Ohno S, Gilchrest BA: The beta isoform of protein kinase C stimulates human melanogenesis by activating tyrosinase in pigment cells. J Biol Chem 1993, 268(16):11742-11749.
48.Mammucari C, Tommasi di Vignano A, Sharov AA, Neilson J, Havrda MC, Roop DR, Botchkarev VA, Crabtree GR, Dotto GP: Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control. Developmental cell 2005, 8(5):665-676.
49.Kuhl M, Sheldahl LC, Malbon CC, Moon RT: Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus. J Biol Chem 2000, 275(17):12701-12711.
50.Pillai S, Bikle DD, Mancianti ML, Cline P, Hincenbergs M: Calcium regulation of growth and differentiation of normal human keratinocytes: modulation of differentiation competence by stages of growth and extracellular calcium. J Cell Physiol 1990, 143(2):294-302.
51.Hernon CA, Harrison CA, Thornton DJ, MacNeil S: Enhancement of keratinocyte performance in the production of tissue-engineered skin using a low-calcium medium. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 2007, 15(5):718-726.
52.Tanaka S, Kato Y: Epigenesis in developing avian scales. I. Qualitative and quantitative characterization of finite cell populations. The Journal of experimental zoology 1983, 225(2):257-269.
53.Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J: A unique chromatin signature uncovers early developmental enhancers in humans. Nature 2011, 470(7333):279-283.
54.Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW et al: Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 2009, 459(7243):108-112.
55.Hardingham GE, Chawla S, Cruzalegui FH, Bading H: Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels. Neuron 1999, 22(4):789-798.
56.Shibasaki M, Mizuno K, Kurokawa K, Ohkuma S: L-type voltage-dependent calcium channels facilitate acetylation of histone H3 through PKCgamma phosphorylation in mice with methamphetamine-induced place preference. Journal of neurochemistry 2011, 118(6):1056-1066.
57.Bikle DD, Xie Z, Tu CL: Calcium regulation of keratinocyte differentiation. Expert review of endocrinology & metabolism 2012, 7(4):461-472.
58.Raya A, Kawakami Y, Rodriguez-Esteban C, Ibanes M, Rasskin-Gutman D, Rodriguez-Leon J, Buscher D, Feijo JA, Izpisua Belmonte JC: Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination. Nature 2004, 427(6970):121-128.
59.Schneider RA: How to tweak a beak: molecular techniques for studying the evolution of size and shape in Darwin''s finches and other birds. BioEssays : news and reviews in molecular, cellular and developmental biology 2007, 29(1):1-6.
60.Kohn AD, Moon RT: Wnt and calcium signaling: beta-catenin-independent pathways. Cell calcium 2005, 38(3-4):439-446.
61.Flentke GR, Garic A, Amberger E, Hernandez M, Smith SM: Calcium-mediated repression of beta-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome. Birth defects research Part A, Clinical and molecular teratology 2011, 91(7):591-602.
62.Rey O, Chang W, Bikle D, Rozengurt N, Young SH, Rozengurt E: Negative cross-talk between calcium-sensing receptor and beta-catenin signaling systems in colonic epithelium. J Biol Chem 2012, 287(2):1158-1167.

Chapter 3
1.Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, Xu J, Moore MJ, Schimenti JC, Weng Z et al: An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell 2013, 50(1):67-81.
2.Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, Popp C, Thienpont B, Dean W, Reik W: The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 2012, 48(6):849-862.
3.Hajkova P: Epigenetic reprogramming in the germline: towards the ground state of the epigenome. Philosophical transactions of the Royal Society of London Series B, Biological sciences 2011, 366(1575):2266-2273.
4.Walsh CP, Chaillet JR, Bestor TH: Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nature genetics 1998, 20(2):116-117.
5.Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA: Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 2002, 117(1-2):15-23.
6.Kidwell MG, Holyoake AJ: Transposon-induced hotspots for genomic instability. Genome research 2001, 11(8):1321-1322.
7.Lin H, Spradling AC: A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 1997, 124(12):2463-2476.
8.Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H: A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes & development 1998, 12(23):3715-3727.
9.Thomson T, Lin H: The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annual review of cell and developmental biology 2009, 25:355-376.
10.Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ: Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 2007, 128(6):1089-1103.
11.Deng W, Lin H: miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Developmental cell 2002, 2(6):819-830.
12.Kuramochi-Miyagawa S, Kimura T, Ijiri TW, Isobe T, Asada N, Fujita Y, Ikawa M, Iwai N, Okabe M, Deng W et al: Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development 2004, 131(4):839-849.
13.Carmell MA, Girard A, van de Kant HJ, Bourc''his D, Bestor TH, de Rooij DG, Hannon GJ: MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Developmental cell 2007, 12(4):503-514.
14.Unhavaithaya Y, Hao Y, Beyret E, Yin H, Kuramochi-Miyagawa S, Nakano T, Lin H: MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation. J Biol Chem 2009, 284(10):6507-6519.
15.Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T et al: MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Developmental cell 2011, 20(3):364-375.
16.Parker JS, Roe SM, Barford D: Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature 2005, 434(7033):663-666.
17.Feltzin VL, Khaladkar M, Abe M, Parisi M, Hendriks GJ, Kim J, Bonini NM: The exonuclease Nibbler regulates age-associated traits and modulates piRNA length in Drosophila. Aging Cell 2015, 14(3):443-452.
18.Czech B, Hannon GJ: A Happy 3'' Ending to the piRNA Maturation Story. Cell 2016, 164(5):838-840.
19.Anastasakis D, Skeparnias I, Shaukat AN, Grafanaki K, Kanellou A, Taraviras S, Papachristou DJ, Papakyriakou A, Stathopoulos C: Mammalian PNLDC1 is a novel poly(A) specific exonuclease with discrete expression during early development. Nucleic Acids Res 2016, 44(18):8908-8920.
20.Saito K, Sakaguchi Y, Suzuki T, Suzuki T, Siomi H, Siomi MC: Pimet, the Drosophila homolog of HEN1, mediates 2''-O-methylation of Piwi- interacting RNAs at their 3'' ends. Genes & development 2007, 21(13):1603-1608.
21.Kirino Y, Mourelatos Z: Mouse Piwi-interacting RNAs are 2''-O-methylated at their 3'' termini. Nat Struct Mol Biol 2007, 14(4):347-348.
22.Kirino Y, Mourelatos Z: The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs. Rna 2007, 13(9):1397-1401.
23.Khurana JS, Theurkauf W: piRNAs, transposon silencing, and Drosophila germline development. J Cell Biol 2010, 191(5):905-913.
24.Juliano C, Wang J, Lin H: Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annual review of genetics 2011, 45:447-469.
25.Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ: Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 2007, 316(5825):744-747.
26.Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M, Funaya C, Antony C, Sachidanandam R, Pillai RS: Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing. Nature 2011, 480(7376):264-267.
27.De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O''Carroll D: The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 2011, 480(7376):259-263.
28.Czech B, Hannon GJ: One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-Guided Silencing. Trends Biochem Sci 2016, 41(4):324-337.
29.Aravin AA, Bourc''his D: Small RNA guides for de novo DNA methylation in mammalian germ cells. Genes & development 2008, 22(8):970-975.
30.Aravin AA, Sachidanandam R, Bourc''his D, Schaefer C, Pezic D, Toth KF, Bestor T, Hannon GJ: A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 2008, 31(6):785-799.
31.Pezic D, Manakov SA, Sachidanandam R, Aravin AA: piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes & development 2014, 28(13):1410-1428.
32.Zamudio N, Barau J, Teissandier A, Walter M, Borsos M, Servant N, Bourc''his D: DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination. Genes & development 2015, 29(12):1256-1270.
33.Tseng YT, Liao HF, Yu CY, Mo CF, Lin SP: Epigenetic factors in the regulation of prospermatogonia and spermatogonial stem cells. Reproduction 2015, 150(3):R77-91.
34.Kojima-Kita K, Kuramochi-Miyagawa S, Nagamori I, Ogonuki N, Ogura A, Hasuwa H, Akazawa T, Inoue N, Nakano T: MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells. Cell Rep 2016, 16(11):2819-2828.
35.Iwasaki YW, Siomi MC, Siomi H: PIWI-Interacting RNA: Its Biogenesis and Functions. Annu Rev Biochem 2015, 84:405-433.
36.Bao J, Zhang Y, Schuster AS, Ortogero N, Nilsson EE, Skinner MK, Yan W: Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for prospermatogonial development in mice. Cell Death Differ 2014, 21(5):783-796.
37.Gerdes P, Richardson SR, Mager DL, Faulkner GJ: Transposable elements in the mammalian embryo: pioneers surviving through stealth and service. Genome biology 2016, 17:100.
38.Rengaraj D, Lee SI, Park TS, Lee HJ, Kim YM, Sohn YA, Jung M, Noh SJ, Jung H, Han JY: Small non-coding RNA profiling and the role of piRNA pathway genes in the protection of chicken primordial germ cells. BMC Genomics 2014, 15:757.
39.Xu L, Qiu L, Chang G, Guo Q, Liu X, Bi Y, Zhang Y, Wang H, Li Z, Guo X et al: Discovery of piRNAs Pathway Associated with Early-Stage Spermatogenesis in Chicken. PLoS One 2016, 11(4):e0151780.
40.Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL: TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome biology 2013, 14(4):R36.
41.Nawrocki EP, Burge SW, Bateman A, Daub J, Eberhardt RY, Eddy SR, Floden EW, Gardner PP, Jones TA, Tate J et al: Rfam 12.0: updates to the RNA families database. Nucleic Acids Res 2015, 43(Database issue):D130-137.
42.Aken BL, Ayling S, Barrell D, Clarke L, Curwen V, Fairley S, Fernandez Banet J, Billis K, Garcia Giron C, Hourlier T et al: The Ensembl gene annotation system. Database (Oxford) 2016, 2016.
43.Kozomara A, Griffiths-Jones S: miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 2014, 42(Database issue):D68-73.
44.Friedlander MR, Chen W, Adamidi C, Maaskola J, Einspanier R, Knespel S, Rajewsky N: Discovering microRNAs from deep sequencing data using miRDeep. Nature biotechnology 2008, 26(4):407-415.
45.Langmead B, Salzberg SL: Fast gapped-read alignment with Bowtie 2. Nature methods 2012, 9(4):357-359.
46.Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L: Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature biotechnology 2010, 28(5):511-515.
47.Roberts A, Pimentel H, Trapnell C, Pachter L: Identification of novel transcripts in annotated genomes using RNA-Seq. Bioinformatics 2011, 27(17):2325-2329.
48.Rosenkranz D, Zischler H: proTRAC--a software for probabilistic piRNA cluster detection, visualization and analysis. BMC Bioinformatics 2012, 13:5.
49.Zhang Z, Wang J, Schultz N, Zhang F, Parhad SS, Tu S, Vreven T, Zamore PD, Weng Z, Theurkauf WE: The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 2014, 157(6):1353-1363.
50.Vokes SA, Ji H, Wong WH, McMahon AP: A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb. Genes & development 2008, 22(19):2651-2663.
51.Hussein SM, Puri MC, Tonge PD, Benevento M, Corso AJ, Clancy JL, Mosbergen R, Li M, Lee DS, Cloonan N et al: Genome-wide characterization of the routes to pluripotency. Nature 2014, 516(7530):198-206.
52.Goriaux C, Desset S, Renaud Y, Vaury C, Brasset E: Transcriptional properties and splicing of the flamenco piRNA cluster. EMBO Rep 2014, 15(4):411-418.
53.Weick EM, Miska EA: piRNAs: from biogenesis to function. Development 2014, 141(18):3458-3471.
54.Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK: Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 2010, 38(4):576-589.
55.Whyte J, Glover JD, Woodcock M, Brzeszczynska J, Taylor L, Sherman A, Kaiser P, McGrew MJ: FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self-Renewal. Stem Cell Reports 2015, 5(6):1171-1182.
56.Crooks GE, Hon G, Chandonia JM, Brenner SE: WebLogo: a sequence logo generator. Genome research 2004, 14(6):1188-1190.
57.Swift CH: Origin of the sex-cords and definitive spermatogonia in the male chick. Am J Anat 1916, 20(3):375-410.
58.Aquila S, Bonofiglio D, Gentile M, Middea E, Gabriele S, Belmonte M, Catalano S, Pellegrino M, Ando S: Peroxisome proliferator-activated receptor (PPAR)gamma is expressed by human spermatozoa: its potential role on the sperm physiology. J Cell Physiol 2006, 209(3):977-986.
59.Liu LL, Xian H, Cao JC, Zhang C, Zhang YH, Chen MM, Qian Y, Jiang M: Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology. Asian J Androl 2015, 17(6):942-947.
60.Barchi M, Geremia R, Magliozzi R, Bianchi E: Isolation and analyses of enriched populations of male mouse germ cells by sedimentation velocity: the centrifugal elutriation. Methods Mol Biol 2009, 558:299-321.
61.Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, Koplev S, Jenkins SL, Jagodnik KM, Lachmann A et al: Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 2016, 44(W1):W90-97.
62.Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, Asada N, Kojima K, Yamaguchi Y, Ijiri TW et al: DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes & development 2008, 22(7):908-917.
63.Manakov SA, Pezic D, Marinov GK, Pastor WA, Sachidanandam R, Aravin AA: MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation. Cell Rep 2015, 12(8):1234-1243.
64.Lee YC: The Role of piRNA-Mediated Epigenetic Silencing in the Population Dynamics of Transposable Elements in Drosophila melanogaster. PLoS genetics 2015, 11(6):e1005269.
65.Beyret E, Liu N, Lin H: piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell research 2012, 22(10):1429-1439.
66.Vourekas A, Zheng Q, Alexiou P, Maragkakis M, Kirino Y, Gregory BD, Mourelatos Z: Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat Struct Mol Biol 2012, 19(8):773-781.
67.Herquel B, Ouararhni K, Martianov I, Le Gras S, Ye T, Keime C, Lerouge T, Jost B, Cammas F, Losson R et al: Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA. Nat Struct Mol Biol 2013, 20(3):339-346.
68.Young JM, Whiddon JL, Yao Z, Kasinathan B, Snider L, Geng LN, Balog J, Tawil R, van der Maarel SM, Tapscott SJ: DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis. PLoS genetics 2013, 9(11):e1003947.
69.Pavlicev M, Hiratsuka K, Swaggart KA, Dunn C, Muglia L: Detecting endogenous retrovirus-driven tissue-specific gene transcription. Genome Biol Evol 2015, 7(4):1082-1097.
70.Glinsky GV: Transposable Elements and DNA Methylation Create in Embryonic Stem Cells Human-Specific Regulatory Sequences Associated with Distal Enhancers and Noncoding RNAs. Genome Biol Evol 2015, 7(6):1432-1454.
71.Rangan P, Malone CD, Navarro C, Newbold SP, Hayes PS, Sachidanandam R, Hannon GJ, Lehmann R: piRNA production requires heterochromatin formation in Drosophila. Curr Biol 2011, 21(16):1373-1379.
72.Jean C, Oliveira NM, Intarapat S, Fuet A, Mazoyer C, De Almeida I, Trevers K, Boast S, Aubel P, Bertocchini F et al: Transcriptome analysis of chicken ES, blastodermal and germ cells reveals that chick ES cells are equivalent to mouse ES cells rather than EpiSC. Stem Cell Res 2015, 14(1):54-67.
73.Acampora D, Di Giovannantonio LG, Simeone A: Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition. Development 2013, 140(1):43-55.
74.Osorio KM, Lee SE, McDermitt DJ, Waghmare SK, Zhang YV, Woo HN, Tumbar T: Runx1 modulates developmental, but not injury-driven, hair follicle stem cell activation. Development 2008, 135(6):1059-1068.
75.Osorio KM, Lilja KC, Tumbar T: Runx1 modulates adult hair follicle stem cell emergence and maintenance from distinct embryonic skin compartments. J Cell Biol 2011, 193(1):235-250.
76.Smith E, Sigvardsson M: The roles of transcription factors in B lymphocyte commitment, development, and transformation. J Leukoc Biol 2004, 75(6):973-981.
77.Azcoitia V, Aracil M, Martinez AC, Torres M: The homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo. Developmental biology 2005, 280(2):307-320.
78.Tilgner K, Atkinson SP, Golebiewska A, Stojkovic M, Lako M, Armstrong L: Isolation of primordial germ cells from differentiating human embryonic stem cells. Stem Cells 2008, 26(12):3075-3085.
79.Wongtrakoongate P, Jones M, Gokhale PJ, Andrews PW: STELLA facilitates differentiation of germ cell and endodermal lineages of human embryonic stem cells. PLoS One 2013, 8(2):e56893.
80.Li BC, Tian ZQ, Sun M, Xu Q, Wang XY, Qin YR, Xu F, Gao B, Wang KH, Sun HC et al: Directional differentiation of chicken primordial germ cells into adipocytes, neuron-like cells, and osteoblasts. Mol Reprod Dev 2010, 77(9):795-801.
81.Kress C, Montillet G, Jean C, Fuet A, Pain B: Chicken embryonic stem cells and primordial germ cells display different heterochromatic histone marks than their mammalian counterparts. Epigenetics Chromatin 2016, 9:5.
82.Ben-Ari Fuchs S, Lieder I, Stelzer G, Mazor Y, Buzhor E, Kaplan S, Bogoch Y, Plaschkes I, Shitrit A, Rappaport N et al: GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data. OMICS 2016, 20(3):139-151.
83.Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S et al: Generation of pluripotent stem cells from neonatal mouse testis. Cell 2004, 119(7):1001-1012.
84.Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W et al: Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 2006, 440(7088):1199-1203.
85.Huang YH, Chin CC, Ho HN, Chou CK, Shen CN, Kuo HC, Wu TJ, Wu YC, Hung YC, Chang CC et al: Pluripotency of mouse spermatogonial stem cells maintained by IGF-1- dependent pathway. FASEB J 2009, 23(7):2076-2087.
86.Li B, Wang XY, Tian Z, Xiao XJ, Xu Q, Wei CX, Y F, Sun HC, Chen GH: Directional differentiation of chicken spermatogonial stem cells in vitro. Cytotherapy 2010, 12(3):326-331.
87.Wang X, Chen T, Zhang Y, Li B, Xu Q, Song C: Isolation and Culture of Pig Spermatogonial Stem Cells and Their in Vitro Differentiation into Neuron-Like Cells and Adipocytes. Int J Mol Sci 2015, 16(11):26333-26346.
88.Azizi H, Conrad S, Hinz U, Asgari B, Nanus D, Peterziel H, Hajizadeh Moghaddam A, Baharvand H, Skutella T: Derivation of Pluripotent Cells from Mouse SSCs Seems to Be Age Dependent. Stem Cells Int 2016, 2016:8216312.

Chapter 4
1.Chirn GW, Rahman R, Sytnikova YA, Matts JA, Zeng M, Gerlach D, Yu M, Berger B, Naramura M, Kile BT et al: Conserved piRNA Expression from a Distinct Set of piRNA Cluster Loci in Eutherian Mammals. PLoS genetics 2015, 11(11):e1005652.
2.Sharma AK, Nelson MC, Brandt JE, Wessman M, Mahmud N, Weller KP, Hoffman R: Human CD34(+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood 2001, 97(2):426-434.
3.Lee EJ, Banerjee S, Zhou H, Jammalamadaka A, Arcila M, Manjunath BS, Kosik KS: Identification of piRNAs in the central nervous system. Rna 2011, 17(6):1090-1099.
4.Wu Q, Ma Q, Shehadeh LA, Wilson A, Xia L, Yu H, Webster KA: Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells. Biochem Biophys Res Commun 2010, 396(4):915-920.
5.Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, Xu J, Moore MJ, Schimenti JC, Weng Z et al: An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell 2013, 50(1):67-81.
6.Hedges SB: The origin and evolution of model organisms. Nature reviews Genetics 2002, 3(11):838-849.
7.Reisz RR, Muller J: Molecular timescales and the fossil record: a paleontological perspective. Trends in genetics : TIG 2004, 20(5):237-241.
8.Hughes SH, Greenhouse JJ, Petropoulos CJ, Sutrave P: Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol 1987, 61(10):3004-3012.
9.Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ: Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature methods 2013, 10(12):1213-1218.
10.Hughes MW, Wu P, Jiang TX, Lin SJ, Dong CY, Li A, Hsieh FJ, Widelitz RB, Chuong CM: In search of the Golden Fleece: unraveling principles of morphogenesis by studying the integrative biology of skin appendages. Integrative biology : quantitative biosciences from nano to macro 2011, 3(4):388-407.
11.Brind''Amour J, Liu S, Hudson M, Chen C, Karimi MM, Lorincz MC: An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations. Nat Commun 2015, 6:6033.
12.Horvath P, Barrangou R: CRISPR/Cas, the immune system of bacteria and archaea. Science 2010, 327(5962):167-170.
13.Zhang F, Wen Y, Guo X: CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 2014, 23(R1):R40-46.
14.Cong L, Zhang F: Genome engineering using CRISPR-Cas9 system. Methods Mol Biol 2015, 1239:197-217.
15.Zhang P, Kang JY, Gou LT, Wang J, Xue Y, Skogerboe G, Dai P, Huang DW, Chen R, Fu XD et al: MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell research 2015, 25(2):193-207.
16.Widelitz RB, Jiang TX, Lu J, Chuong CM: beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin. Developmental biology 2000, 219(1):98-114.
17.Bovolenta P, Rodriguez J, Esteve P: Frizzled/RYK mediated signalling in axon guidance. Development 2006, 133(22):4399-4408.
18.Wang Q, Zhou Y, Rychahou P, Liu C, Weiss HL, Evers BM: NFAT5 represses canonical Wnt signaling via inhibition of beta-catenin acetylation and participates in regulating intestinal cell differentiation. Cell Death Dis 2013, 4:e671.
19.Flentke GR, Garic A, Hernandez M, Smith SM: CaMKII represses transcriptionally active beta-catenin to mediate acute ethanol neurodegeneration and can phosphorylate beta-catenin. Journal of neurochemistry 2014, 128(4):523-535.
20.Girard A, Sachidanandam R, Hannon GJ, Carmell MA: A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 2006, 442(7099):199-202.
21.Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, Asada N, Kojima K, Yamaguchi Y, Ijiri TW et al: DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes & development 2008, 22(7):908-917.
22.Molaro A, Falciatori I, Hodges E, Aravin AA, Marran K, Rafii S, McCombie WR, Smith AD, Hannon GJ: Two waves of de novo methylation during mouse germ cell development. Genes & development 2014, 28(14):1544-1549.
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