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Stabilization of mouse haploid embryonic stem cells with combined kinase and signal modulation.


ABSTRACT: Mammalian haploid embryonic stem cells (haESCs) provide new possibilities for large-scale genetic screens because they bear only one copy of each chromosome. However, haESCs are prone to spontaneous diploidization through unknown mechanisms. Here, we report that a small molecule combination could restrain mouse haESCs from diploidization by impeding exit from naïve pluripotency and by shortening the S-G2/M phases. Combined with 2i and PD166285, our chemical cocktail could maintain haESCs in the haploid state for at least five weeks without fluorescence-activated cell sorting (FACS) enrichment of haploid cells. Taken together, we established an effective chemical approach for long-term maintenance of haESCs, and highlighted that proper cell cycle progression was critical for the maintenance of haploid state.

SUBMITTER: Li H 

PROVIDER: S-EPMC5643530 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Stabilization of mouse haploid embryonic stem cells with combined kinase and signal modulation.

Li Haisen H   Guo Ao A   Xie Zhenfei Z   Tu Wanzhi W   Yu Jiali J   Wang Huihan H   Zhao Jian J   Zhong Cuiqing C   Kang Jiuhong J   Li Jinsong J   Huang Shichao S   Shen Li L  

Scientific reports 20171016 1


Mammalian haploid embryonic stem cells (haESCs) provide new possibilities for large-scale genetic screens because they bear only one copy of each chromosome. However, haESCs are prone to spontaneous diploidization through unknown mechanisms. Here, we report that a small molecule combination could restrain mouse haESCs from diploidization by impeding exit from naïve pluripotency and by shortening the S-G2/M phases. Combined with 2i and PD166285, our chemical cocktail could maintain haESCs in the  ...[more]

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