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

Open access
Guo, Jingtao, Grow, Edward J., Yi, Chongil, Mlcochova, Hana, Maher, Geoffrey J., Lindskog, Cecilia, Murphy, Patrick J., Wike, Candice L., Carrell, Douglas T., Goriely, Anne, Hotaling, James M., Cairns, Bradley R.·2017·Cell Stem Cell

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, 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.

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Metadata

Authors
Guo, J., Grow, E. J., Yi, C., Mlcochova, H., Maher, G. J., Lindskog, C., Murphy, P. J., Wike, C. L., Carrell, D. T., Goriely, A., Hotaling, J. M., & Cairns, B. R.
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2017-10
Volume
21
Issue
4
Pages
533-546.e6
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2763109317
Cited by
295
References
10
FWCI
26.76
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development. https://app.cochat.ai/papers/10.1016/j.stem.2017.09.003
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Guo, J., Grow, E. J., Yi, C., Mlcochova, H., Maher, G. J., Lindskog, C., Murphy, P. J., Wike, C. L., Carrell, D. T., Goriely, A., Hotaling, J. M., & Cairns, B. R. (2017). Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development. Cell Stem Cell. https://doi.org/10.1016/j.stem.2017.09.003

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.