Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2017
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| _version_ | 1826278352534634496 |
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| author | Guo, J Grow, E Yi, C Mlcochova, H Maher, G Lindskog, C Murphy, P Wike, C Carrell, D Goriely, A Hotaling, J Cairns, B |
| author_facet | Guo, J Grow, E Yi, C Mlcochova, H Maher, G Lindskog, C Murphy, P Wike, C Carrell, D Goriely, A Hotaling, J Cairns, B |
| author_sort | Guo, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:42:39Z |
| format | Journal article |
| id | oxford-uuid:6fd6e57e-5105-47ac-81d3-a9483f3ac468 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:42:39Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:6fd6e57e-5105-47ac-81d3-a9483f3ac4682022-03-26T19:33:21ZChromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell developmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6fd6e57e-5105-47ac-81d3-a9483f3ac468EnglishSymplectic Elements at OxfordElsevier2017Guo, JGrow, EYi, CMlcochova, HMaher, GLindskog, CMurphy, PWike, CCarrell, DGoriely, AHotaling, JCairns, BHuman 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. |
| spellingShingle | Guo, J Grow, E Yi, C Mlcochova, H Maher, G Lindskog, C Murphy, P Wike, C Carrell, D Goriely, A Hotaling, J Cairns, B Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
| title | Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
| title_full | Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
| title_fullStr | Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
| title_full_unstemmed | Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
| title_short | Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
| title_sort | chromatin and single cell rna seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development |
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