Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells

• 作者: Chenglei Tian Linlin Liu Ming Zeng Xiaoyan Sheng Dai Heng Lingling Wang Xiaoying Ye David L.Keefe Lin Liu
• 来源期刊: 蛋白质与细胞
• 年，卷（期）: 2021,（12）
• 所属期刊栏目: RESEARCH ARTICLE
• 页码范围: 947-964
• 页数: 18页
• 语种: 英文

摘要

Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained without genetic manipulation from partheno-genetic embryonic stem cells (pESCs) derived from parthenogenetic embryos,presumably attributable to their aberrant imprinting.We show that an unlimited number of oocytes can be derived from pESCs and pro-duce healthy offspring.Moreover,normal expression of imprinted genes is found in the germ cells and the mice.pESCs exhibited imprinting consistent with exclusively maternal lineage,and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background.pESCs differentiated into primordial germ cell-like cells (PGCLCs) and formed oocytes fol-lowing in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endo-crine function.The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs,consistent with efficient reprogramming of methylation and genomic imprinting.These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting,offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.