Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro  

作　　者：Ling Shuai Yukai Wang Mingzhu Dong Xuepeng Wang Lisi Sang Mei Wang Haifeng Wan Guanzheng Luo Tiantian Gu Yan Yuan Chunjing Feng Fei Teng Wei Li Xiuying Liu Tianda Li Liu Wang Xiu-Jie Wang Xiao-Yang Zhao Qi Zhou 

机构地区：[1]State Key Laboratory of Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [2]Graduate School of Chinese Academy of Sciences,Beijing 100049,China [3]College of Life Sciences,Hunan Normal University,Changsha 410081,China [4]Center for Molecular Systems Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China [5]State Key Laboratory of Reproductive Medicine,Department of Histology and Embryology,Nanjing Medical University,Nanjing 210029,China

出　　处：《Journal of Molecular Cell Biology》2015年第4期326-337,共12页分子细胞生物学报（英文版）

基　　金：supported by grants from the National Basic Research Program of China(2012CBA01300 to Q.Z.and 2014CB964800 to W.L.);the National Science Foundation of China(91319308 to Q.Z.).

摘　　要：Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.

关 键 词：HAPLOID epiblast stem cells durable pluripotency 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]