Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells.

TitleEpigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsLiu Y, Giannopoulou EG, Wen D, Falciatori I, Elemento O, C Allis D, Rafii S, Seandel M
JournalNat Commun
Date Published2016 04 27
KeywordsAnimals, Cell Differentiation, Cell Plasticity, Cells, Cultured, Embryonic Stem Cells, Epigenomics, Gene Expression Profiling, Histones, Lysine, Male, Methylation, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Transgenic, Multipotent Stem Cells, Spermatogenesis, Spermatogonia

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of germ cell-specific gene expression and initiation of embryonic-like programs. Furthermore, SSCs in vitro maintain the epigenomic characteristics of germ cells in vivo. Our observations suggest that SSCs encode innate plasticity through the epigenome and that both conversion of promoter chromatin states and activation of cell type-specific enhancers are prominent features of reprogramming.

Alternate JournalNat Commun
PubMed ID27117588
PubMed Central IDPMC4853422
Grant ListR01 HL115128 / HL / NHLBI NIH HHS / United States
R01 HL128158 / HL / NHLBI NIH HHS / United States
R01 DK095039 / DK / NIDDK NIH HHS / United States
DP2 HD080352 / HD / NICHD NIH HHS / United States
R01 HL119872 / HL / NHLBI NIH HHS / United States