Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development.

ABSTRACT: Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4⁺ hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4⁺ hSSCs and differentiating c-KIT⁺ spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed. Interestingly, open chromatin in hSSCs was strikingly enriched in binding sites for pioneer factors (NFYA/B, DMRT1, and hormone receptors). Remarkably,

SUBMITTER: Guo J 

PROVIDER: S-EPMC5832720 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature