哺乳动物单倍体胚胎干细胞的建立与应用  

Generation and applications of mammalian haploid embryonic stem cells

作　　者：丁一夫 李劲松 周琪[2] DING YiFu;LI JinSong;ZHOU Qi(State Key Laboratory of Cell Biology,CAS Center for Excellence in Molecular Cell Science,Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,Shanghai 200031,China;State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China)

机构地区：[1]中国科学院分子细胞科学卓越创新中心(生物化学与细胞生物学研究所),细胞生物学国家重点实验室,上海200031 [2]中国科学院动物研究所,干细胞与生殖生物学国家重点实验室,北京100101

出　　处：《中国科学：生命科学》2019年第12期1635-1651,共17页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:31530048,81672117,31730062)资助

摘　　要：哺乳动物胚胎干细胞通常为二倍体,限制了其在后基因组时代功能基因研究上的应用.近年来,随着不同物种单倍体胚胎干细胞的建立,科学家获得了一种可用于高通量正反向遗传筛选的细胞工具.单倍体胚胎干细胞具有类似于二倍体胚胎干细胞的无限增殖能力、基因表达模式、分化潜能等特点,可以在细胞水平开展遗传筛选研究;通过不同物种单倍体干细胞的融合形成异源二倍体细胞可以用于研究基因的演化.另外,小鼠单倍体胚胎干细胞可代替配子用于产生动物,这为研究基因印记在胚胎发育过程中的作用、快速构建携带复杂基因修饰的模式动物、进行个体水平遗传筛选等提供了一个新的遗传学工具.最近,单倍体胚胎干细胞的基因组标签计划的提出,以构建所有编码蛋白质基因的标签小鼠资源平台为目的,将促进蛋白质研究的标准化,并为揭开胚胎发育复杂而有序的蛋白质调控网络提供工具.Mammalian embryonic stem cells(ESCs) are usually diploid, which greatly limit their applications in genetic studies due to existence of two copies of each gene. Recently, the haploid embryonic stem cells(haESCs) have been established from different species,enabling large-scale forward or reverse genetic screening in mammals. The haESCs, same as diploid ESCs, sustain the abilities of self-renewal, proliferation and differentiation, greatly enhancing genetic analyses at the cellular level. Meanwhile, the allodiploid ESCs derived by fusion of haESCs from mice and rats provide a unique system to study the evolution of genes. Besides, the ability of mouse haESCs that can be used as sperm replacement for generation of animals opens new avenues for functional genetics in vivo,such as investigating the roles of imprinted genes during prenatal embryonic development, generation of mouse models carrying complex gene modifications to mimic human diseases and screening for critical genes or amino acids of a specific protein involved in a developmental process of interest. Genome Tagging Project(GTP) proposed based on haESCs was initiated recently with the goal to tag every protein in haESCs, followed by generation of tagged mice at genome-wide scale. GTP will provide a standard platform for the protein study, which may enable precise description of protein atlas and regulatory networks during embryonic development.

关 键 词：单倍体胚胎干细胞 遗传筛选 异源二倍体胚胎干细胞 “人造精子细胞” 基因组标签计划 

分 类 号：Q813[生物学—生物工程]