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Chromatin and Single-Cell RNA- Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development
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- Guo, Jingtao (author)
- Univ Utah, Sch Med, Dept Oncol Sci, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA.;Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
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- Grow, Edward J. (author)
- Univ Utah, Sch Med, Dept Oncol Sci, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA.;Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
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- Yi, Chongil (author)
- Univ Utah, Sch Med, Dept Oncol Sci, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA.;Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
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- Univ Utah, Sch Med, Dept Oncol Sci, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA;Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Univ Oxford, Radcliffe Dept Med, MRC Weatherall Inst Mol Med, Oxford OX3 9DS, England. (creator_code:org_t)
- CELL PRESS, 2017
- 2017
- English.
- In: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 21:4, s. 533-546
- Journal article (peer-reviewed)
Abstract
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- 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, single-cell RNA-seq clustering analysis identified four cellular/developmental states during hSSC differentiation, involving major transitions in cell-cycle and transcriptional regulators, splicing and signaling factors, and glucose/mitochondria regulators. Overall, our results outline the dynamic chromatin/transcription landscape operating in hSSCs and identify crucial molecular pathways that accompany the transition from quiescence to proliferation and differentiation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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