2. Academic Validation
  3. BCL2 is a major regulator of haploidy maintenance in murine embryonic stem cells

BCL2 is a major regulator of haploidy maintenance in murine embryonic stem cells

  • Cell Prolif. 2023 May 5;e13498. doi: 10.1111/cpr.13498.
Shengyi Sun 1,  Qin Zhao 1,  Yiding Zhao 1,  Mengyang Geng 1,  Qing Wang 1,  Qian Gao 1,  Xiao-Ou Zhang 2,  Wenhao Zhang 1 3,  Ling Shuai 1 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Central Hospital of Gynecology Obstetrics/Tianjin Key Laboratory of Human Development and Reproductive Regulation, Nankai University, Tianjin, China.
  • 2 Shanghai Key Laboratory of Maternal and Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life and Science and Technology, Tongji University, Shanghai, China.
  • 3 Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Health Center for Women and Children, Chongqing, China.
  • 4 National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
PMID: 37144356 DOI: 10.1111/cpr.13498
Abstract

Mammalian haploid cells are important resources for forward genetic screening and are important in genetic medicine and drug development. However, the self-diploidization of murine haploid embryonic stem cells (haESCs) during daily culture or differentiation jeopardizes their use in genetic approaches. Here, we show that overexpression (OE) of an antiapoptosis gene, BCL2, in haESCs robustly ensures their haploidy maintenance in various situations, even under strict differentiation in vivo (embryonic 10.5 chimeric fetus or 21-day teratoma). Haploid cell lines of many lineages, including epiblasts, trophectodermal lineages, and neuroectodermal lineages, can be easily derived by the differentiation of BCL2-OE haESCs in vitro. Transcriptome analysis revealed that BCL2-OE activates another regulatory gene, Has2, which is also sufficient for haploidy maintenance. Together, our findings provide an effective and secure strategy to reduce diploidization during differentiation, which will contribute to the generation of haploid cell lines of the desired lineage and related genetic screening.

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