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

• Published in: Scientific reports 2017-10, Vol.7 (1), p.13222-14, Article 13222
• Main Authors: Li, Haisen, Guo, Ao, Xie, Zhenfei, Tu, Wanzhi, Yu, Jiali, Wang, Huihan, Zhao, Jian, Zhong, Cuiqing, Kang, Jiuhong, Li, Jinsong, Huang, Shichao, Shen, Li
• Format: Article
• Language: English
• Subjects: 13/100; 13/109; 13/2; 13/31; 14/1; 14/19; 14/63; 38/22; 38/23; 38/39; 38/61; 38/77; 38/90; 38/91; 42/35; 631/532/2117; 631/92/613; 64/60; 82/80; 96; 96/98; Cell cycle; Embryo cells; Embryos; Flow cytometry; Genetic screening; Humanities and Social Sciences; multidisciplinary; Pluripotency; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-13471-4

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.