Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells

Many different types of stem cells utilize asymmetric cell division (ACD) to produce two daughter cells with distinct fates. Haspin-catalyzed phosphorylation of histone H3 at Thr3 (H3T3ph) plays important roles during mitosis, including ACD in stem cells. However, whether and how Haspin functions in...

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Autores principales: Gao, Yingying, Ma, Bin, Li, Yifan, Wu, Xiangyu, Zhao, Shifeng, Guo, Huiping, Wang, Yiwei, Sun, Lihua, Xie, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447528/
https://www.ncbi.nlm.nih.gov/pubmed/37612272
http://dx.doi.org/10.1038/s41420-023-01604-w
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author Gao, Yingying
Ma, Bin
Li, Yifan
Wu, Xiangyu
Zhao, Shifeng
Guo, Huiping
Wang, Yiwei
Sun, Lihua
Xie, Jing
author_facet Gao, Yingying
Ma, Bin
Li, Yifan
Wu, Xiangyu
Zhao, Shifeng
Guo, Huiping
Wang, Yiwei
Sun, Lihua
Xie, Jing
author_sort Gao, Yingying
collection PubMed
description Many different types of stem cells utilize asymmetric cell division (ACD) to produce two daughter cells with distinct fates. Haspin-catalyzed phosphorylation of histone H3 at Thr3 (H3T3ph) plays important roles during mitosis, including ACD in stem cells. However, whether and how Haspin functions in ACD regulation remains unclear. Here, we report that Haspin knockout (Haspin-KO) mouse embryonic stem cells (mESCs) had increased ratio of ACD, which cumulatively regulates cell fate decisions. Furthermore, Wnt5a is significantly downregulated due to decreased Pax2 in Haspin-KO mESCs. Wnt5a knockdown mESCs phenocopied Haspin-KO cells while overexpression of Wnt5a in Haspin-KO cells rescued disproportionated ACD. Collectively, Haspin is indispensable for mESCs to maintain a balanced ratio of ACD, which is essential for normal development and homeostasis.
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spelling pubmed-104475282023-08-25 Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells Gao, Yingying Ma, Bin Li, Yifan Wu, Xiangyu Zhao, Shifeng Guo, Huiping Wang, Yiwei Sun, Lihua Xie, Jing Cell Death Discov Article Many different types of stem cells utilize asymmetric cell division (ACD) to produce two daughter cells with distinct fates. Haspin-catalyzed phosphorylation of histone H3 at Thr3 (H3T3ph) plays important roles during mitosis, including ACD in stem cells. However, whether and how Haspin functions in ACD regulation remains unclear. Here, we report that Haspin knockout (Haspin-KO) mouse embryonic stem cells (mESCs) had increased ratio of ACD, which cumulatively regulates cell fate decisions. Furthermore, Wnt5a is significantly downregulated due to decreased Pax2 in Haspin-KO mESCs. Wnt5a knockdown mESCs phenocopied Haspin-KO cells while overexpression of Wnt5a in Haspin-KO cells rescued disproportionated ACD. Collectively, Haspin is indispensable for mESCs to maintain a balanced ratio of ACD, which is essential for normal development and homeostasis. Nature Publishing Group UK 2023-08-23 /pmc/articles/PMC10447528/ /pubmed/37612272 http://dx.doi.org/10.1038/s41420-023-01604-w Text en © The Author(s) 2023 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gao, Yingying
Ma, Bin
Li, Yifan
Wu, Xiangyu
Zhao, Shifeng
Guo, Huiping
Wang, Yiwei
Sun, Lihua
Xie, Jing
Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells
title Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells
title_full Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells
title_fullStr Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells
title_full_unstemmed Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells
title_short Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells
title_sort haspin balances the ratio of asymmetric cell division through wnt5a and regulates cell fate decisions in mouse embryonic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447528/
https://www.ncbi.nlm.nih.gov/pubmed/37612272
http://dx.doi.org/10.1038/s41420-023-01604-w
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