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Chromatin and Singl...
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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- Mlcochova, Hana (author)
- Univ Oxford, Radcliffe Dept Med, MRC Weatherall Inst Mol Med, Oxford OX3 9DS, England.
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- Maher, Geoffrey J. (author)
- Univ Oxford, Radcliffe Dept Med, MRC Weatherall Inst Mol Med, Oxford OX3 9DS, England.
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- Lindskog, Cecilia (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Murphy, Patrick 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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- Wike, Candice L. (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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- Carrell, Douglas T. (author)
- Univ Utah, Hlth Sci Ctr, Ctr Reconstruct Urol & Mens Hlth, Dept Surg Androl Urol, Salt Lake City, UT 84122 USA.
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- Goriely, Anne (author)
- Univ Oxford, Radcliffe Dept Med, MRC Weatherall Inst Mol Med, Oxford OX3 9DS, England.
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- Hotaling, James M. (author)
- Univ Utah, Hlth Sci Ctr, Ctr Reconstruct Urol & Mens Hlth, Dept Surg Androl Urol, Salt Lake City, UT 84122 USA.
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- Cairns, Bradley R. (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.
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In: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 21:4, s. 533-546
- Related links:
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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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)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Guo, Jingtao
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Grow, Edward J.
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Yi, Chongil
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Mlcochova, Hana
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Maher, Geoffrey ...
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Lindskog, Cecili ...
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show more...
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Murphy, Patrick ...
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Wike, Candice L.
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Carrell, Douglas ...
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Goriely, Anne
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Hotaling, James ...
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Cairns, Bradley ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell Stem Cell
- By the university
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Uppsala University