State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell biology, Chinese Academy of Sciences, Shanghai, 200031, China.
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, 20892, USA.
Sci Rep. 2017 Oct 16;7(1):13222. 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.
哺乳动物单倍体胚胎干细胞（haESCs）由于只携带每条染色体的一个拷贝，因此为大规模遗传筛选提供了新的可能性。然而，haESCs 容易通过未知机制自发二倍体化。在这里，我们报告说，一种小分子组合可以通过阻止幼稚多能性的退出和缩短 S-G2/M 期来阻止小鼠 haESCs 的二倍体化。与 2i 和 PD166285 联合使用，我们的化学鸡尾酒可以在没有荧光激活细胞分选（FACS）富集 haploid 细胞的情况下，至少维持 haESCs 的单倍体状态五周。总之，我们建立了一种有效的化学方法来长期维持 haESCs，并强调适当的细胞周期进程对于维持单倍体状态至关重要。
