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Epigenetic and Transcriptome Dynamics in Spermatogonial Stem Cell Development
Author(s) -
Liao Jason,
Ng Shuk Han,
Chan WaiYee,
Lee TinLap
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.877.3
Subject(s) - biology , dna methylation , transcriptome , epigenetics , epigenome , stem cell , reprogramming , progenitor cell , microbiology and biotechnology , regulation of gene expression , epigenomics , cellular differentiation , gene , genetics , gene expression
Continual spermatogenesis relies on maintenance of spermatogonial stem cells (SSCs) that either self‐renew to sustain a pool of stem cells or differentiate to produce progenitor spermatogonia. Currently, the mechanisms regulating these processes in the mammalian germ line remain largely unknown. Emerging evidence has suggested that epigenetic profiles in SSC shift dramatically when SSC commits to differentiate, and such change is concordant with c‐Kit expression. Epigenetic modifications on DNA methylation and demethylation pathways through formation of 5‐methylcytosine (5mC) and 5‐Hydroxymethylcytosine (5hmC) have profound influences on developmental programs, but its role remains elusive in mammalian spermatogenesis. In this study, we examined the dynamics of DNA methylation and gene expression in undifferentiated and differentiating SSCs by performing RNA‐seq and whole genome 5mC/5hmC profiling at single‐base resolution. We identified signaling and transcriptional difference involving key self‐renewal pathway in undifferentiated and differentiated SSCs and found that differential methylated genes were enriched in various cellular developmental processes. We also observed methylation changes associated with OCT4 and GDNF, which are important for undifferentiated spermatogonia maintenance. Finally, 5hmC was enriched specifically in proximal upstream and downstream regions relative to TSS and its presence correlates positively with gene expression, we found genes enriched in undifferentiated SSCs display higher promoter 5hmC levels, indicating 5hmC is associated with stemness‐related genes and stem cell capacityTaken together, the results provide novel understandings of epigenome and transcriptome dynamics in SSC development.