2. Academic Validation
  3. Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells

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

  • Cell Death Discov. 2023 Aug 23;9(1):307. doi: 10.1038/s41420-023-01604-w.
Yingying Gao 1 2,  Bin Ma 1 3,  Yifan Li 1,  Xiangyu Wu 1,  Shifeng Zhao 4,  Huiping Guo 1,  Yiwei Wang 1,  Lihua Sun 2,  Jing Xie 5 6
Affiliations

Affiliations

  • 1 Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
  • 2 Reproductive Medicine Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
  • 3 Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • 4 Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
  • 5 Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. [email protected].
  • 6 Reproductive Medicine Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. [email protected].
PMID: 37612272 DOI: 10.1038/s41420-023-01604-w
Abstract

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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