The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development
Open accessAbstract
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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Cites
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A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development
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Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
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“FGFR3 is a well-established human spermatogonial marker (Goriely et al., 2009; Maher et al., 2016), whose expression is restricted to a subpopulation of non-proliferating, non-differentiating hSSCs, typically organized in small clusters of two to four cells, that are all SSEA4 (Figure S7A).”
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Construction of a human cell landscape at single-cell level
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The adult human testis transcriptional cell atlas
Guo, J., Grow, E. J., Mlcochova, H., Maher, G. J., Lindskog, C., Nie, X., Guo, Y., Takei, Y., Yun, J., Cai, L., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0099-2 · Cited by 710
Self-citationChromatin accessibility profiling by ATAC-seq
Grandi, F. C., Modi, H., Kampman, L., & Corces, M. R. (2022) · Nature Protocols · doi:10.1038/s41596-022-00692-9 · Cited by 557
Eisenberg, M. L., Esteves, S. C., Lamb, D. J., Hotaling, J. M., Giwercman, A., Hwang, K., & Cheng, Y.-S. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00459-w · Cited by 536
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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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- 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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