Epigenetic Profiles Signify Cell Fate Plasticity in Unipotent Spermatogonial Stem and Progenitor Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 28

PMID 27117588

Citations 23

Authors

Ying Liu

Eugenia G Giannopoulou

Duancheng Wen

Ilaria Falciatori

Olivier Elemento

C David Allis

Shahin Rafii

Marco Seandel

Affiliations

Soon will be listed here.

Abstract

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.

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