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Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development.
- Source :
-
Cell stem cell [Cell Stem Cell] 2017 Oct 05; Vol. 21 (4), pp. 533-546.e6. - Publication Year :
- 2017
-
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 <superscript>+</superscript> hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4 <superscript>+</superscript> hSSCs and differentiating c-KIT <superscript>+</superscript> 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Base Sequence
Binding Sites
Cluster Analysis
DNA metabolism
DNA Methylation genetics
Genomics
Humans
Male
Meiosis
Pluripotent Stem Cells cytology
Pluripotent Stem Cells metabolism
Receptors, Cell Surface metabolism
Repetitive Sequences, Nucleic Acid genetics
Reproducibility of Results
Seminiferous Tubules cytology
Stage-Specific Embryonic Antigens metabolism
Transcription, Genetic
Transcriptome genetics
Chromatin metabolism
Sequence Analysis, RNA methods
Signal Transduction
Single-Cell Analysis methods
Spermatogonia cytology
Stem Cells cytology
Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-9777
- Volume :
- 21
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell stem cell
- Publication Type :
- Academic Journal
- Accession number :
- 28985528
- Full Text :
- https://doi.org/10.1016/j.stem.2017.09.003