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scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells
Spermatogonial stem cells are the most primitive spermatogonia in testis, which can self-renew to maintain the stem cell pool or differentiate to give rise to germ cells including haploid spermatids. All-trans-retinoic acid (RA), a bioactive metabolite of vitamin A, plays a fundamental role in initi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744833/ https://www.ncbi.nlm.nih.gov/pubmed/36509798 http://dx.doi.org/10.1038/s41598-022-25729-7 |
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author | Suen, Hoi Ching Luk, Alfred Chun Shui Liao, Jinyue |
author_facet | Suen, Hoi Ching Luk, Alfred Chun Shui Liao, Jinyue |
author_sort | Suen, Hoi Ching |
collection | PubMed |
description | Spermatogonial stem cells are the most primitive spermatogonia in testis, which can self-renew to maintain the stem cell pool or differentiate to give rise to germ cells including haploid spermatids. All-trans-retinoic acid (RA), a bioactive metabolite of vitamin A, plays a fundamental role in initiating spermatogonial differentiation. In this study, single-cell ATAC-seq (scATAC-seq) was used to obtain genome-wide chromatin maps of cultured germline stem cells (GSCs) that were in control and RA-induced differentiation states. We showed that different subsets of GSCs can be distinguished based on chromatin accessibility of self-renewal and differentiation signature genes. Importantly, both progenitors and a subset of stem cells are able to respond to RA and give rise to differentiating cell subsets with distinct chromatin accessibility profiles. In this study, we identified regulatory regions that undergo chromatin remodeling and are associated with the retinoic signaling pathway. Moreover, we reconstructed the differentiation trajectory and identified novel transcription factor candidates enriched in different spermatogonia subsets. Collectively, our work provides a valuable resource for understanding the heterogeneity associated with differentiation and RA response in GSCs. |
format | Online Article Text |
id | pubmed-9744833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97448332022-12-14 scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells Suen, Hoi Ching Luk, Alfred Chun Shui Liao, Jinyue Sci Rep Article Spermatogonial stem cells are the most primitive spermatogonia in testis, which can self-renew to maintain the stem cell pool or differentiate to give rise to germ cells including haploid spermatids. All-trans-retinoic acid (RA), a bioactive metabolite of vitamin A, plays a fundamental role in initiating spermatogonial differentiation. In this study, single-cell ATAC-seq (scATAC-seq) was used to obtain genome-wide chromatin maps of cultured germline stem cells (GSCs) that were in control and RA-induced differentiation states. We showed that different subsets of GSCs can be distinguished based on chromatin accessibility of self-renewal and differentiation signature genes. Importantly, both progenitors and a subset of stem cells are able to respond to RA and give rise to differentiating cell subsets with distinct chromatin accessibility profiles. In this study, we identified regulatory regions that undergo chromatin remodeling and are associated with the retinoic signaling pathway. Moreover, we reconstructed the differentiation trajectory and identified novel transcription factor candidates enriched in different spermatogonia subsets. Collectively, our work provides a valuable resource for understanding the heterogeneity associated with differentiation and RA response in GSCs. Nature Publishing Group UK 2022-12-12 /pmc/articles/PMC9744833/ /pubmed/36509798 http://dx.doi.org/10.1038/s41598-022-25729-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Suen, Hoi Ching Luk, Alfred Chun Shui Liao, Jinyue scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
title | scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
title_full | scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
title_fullStr | scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
title_full_unstemmed | scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
title_short | scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
title_sort | scatac-seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744833/ https://www.ncbi.nlm.nih.gov/pubmed/36509798 http://dx.doi.org/10.1038/s41598-022-25729-7 |
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