Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.

Spermatogonial stem cells (SSC), the foundation of spermatogenesis and male fertility, possess lifelong self-renewal activity. Aging leads to the decline in stem cell function and increased risk of paternal age-related genetic diseases. In the present study, we performed a comparative genomic analys...

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Autores principales:	Jinyue Liao, Hoi Ching Suen, Alfred Chun Shui Luk, Lele Yang, Annie Wing Tung Lee, Huayu Qi, Tin-Lap Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c278e779c81a487ebacd9f1d601ef7d4
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spelling	oai:doaj.org-article:c278e779c81a487ebacd9f1d601ef7d42021-12-02T20:02:46ZTranscriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.1553-73901553-740410.1371/journal.pgen.1009369https://doaj.org/article/c278e779c81a487ebacd9f1d601ef7d42021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009369https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Spermatogonial stem cells (SSC), the foundation of spermatogenesis and male fertility, possess lifelong self-renewal activity. Aging leads to the decline in stem cell function and increased risk of paternal age-related genetic diseases. In the present study, we performed a comparative genomic analysis of mouse SSC-enriched undifferentiated spermatogonia (Oct4-GFP+/KIT-) and differentiating progenitors (Oct4-GFP+/KIT+) isolated from young and aged testes. Our transcriptome data revealed enormous complexity of expressed coding and non-coding RNAs and alternative splicing regulation during SSC differentiation. Further comparison between young and aged undifferentiated spermatogonia suggested these differentiation programs were affected by aging. We identified aberrant expression of genes associated with meiosis and TGF-β signaling, alteration in alternative splicing regulation and differential expression of specific lncRNAs such as Fendrr. Epigenetic profiling revealed reduced H3K27me3 deposition at numerous pro-differentiation genes during SSC differentiation as well as aberrant H3K27me3 distribution at genes in Wnt and TGF-β signaling upon aging. Finally, aged undifferentiated spermatogonia exhibited gene body hypomethylation, which is accompanied by an elevated 5hmC level. We believe this in-depth molecular analysis will serve as a reference for future analysis of SSC aging.Jinyue LiaoHoi Ching SuenAlfred Chun Shui LukLele YangAnnie Wing Tung LeeHuayu QiTin-Lap LeePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 7, p e1009369 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Jinyue Liao Hoi Ching Suen Alfred Chun Shui Luk Lele Yang Annie Wing Tung Lee Huayu Qi Tin-Lap Lee Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
description	Spermatogonial stem cells (SSC), the foundation of spermatogenesis and male fertility, possess lifelong self-renewal activity. Aging leads to the decline in stem cell function and increased risk of paternal age-related genetic diseases. In the present study, we performed a comparative genomic analysis of mouse SSC-enriched undifferentiated spermatogonia (Oct4-GFP+/KIT-) and differentiating progenitors (Oct4-GFP+/KIT+) isolated from young and aged testes. Our transcriptome data revealed enormous complexity of expressed coding and non-coding RNAs and alternative splicing regulation during SSC differentiation. Further comparison between young and aged undifferentiated spermatogonia suggested these differentiation programs were affected by aging. We identified aberrant expression of genes associated with meiosis and TGF-β signaling, alteration in alternative splicing regulation and differential expression of specific lncRNAs such as Fendrr. Epigenetic profiling revealed reduced H3K27me3 deposition at numerous pro-differentiation genes during SSC differentiation as well as aberrant H3K27me3 distribution at genes in Wnt and TGF-β signaling upon aging. Finally, aged undifferentiated spermatogonia exhibited gene body hypomethylation, which is accompanied by an elevated 5hmC level. We believe this in-depth molecular analysis will serve as a reference for future analysis of SSC aging.
format	article
author	Jinyue Liao Hoi Ching Suen Alfred Chun Shui Luk Lele Yang Annie Wing Tung Lee Huayu Qi Tin-Lap Lee
author_facet	Jinyue Liao Hoi Ching Suen Alfred Chun Shui Luk Lele Yang Annie Wing Tung Lee Huayu Qi Tin-Lap Lee
author_sort	Jinyue Liao
title	Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
title_short	Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
title_full	Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
title_fullStr	Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
title_full_unstemmed	Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
title_sort	transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c278e779c81a487ebacd9f1d601ef7d4
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_version_	1718375684954390528

Transcriptomic and epigenomic profiling of young and aged spermatogonial stem cells reveals molecular targets regulating differentiation.

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