State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; College of Life Science, Northeast Agricultural University, Harbin 150030, China.
Cell Rep. 2019 Jan 8;26(2):407-414.e5. doi: 10.1016/j.celrep.2018.12.067.
Trophoblast stem (TS) cells are increasingly used as a model system for studying placentation and placental disorders. However, practical limitations of genetic manipulation have posed challenges for genetic analysis using TS cells. Here, we report the generation of mouse parthenogenetic haploid TS cells (haTSCs) and show that supplementation with FGF4 and inhibition of Rho-associated protein kinase (ROCK) enable the maintenance of their haploidy and developmental potential. The resulting haTSCs have 20 chromosomes, exhibit typical expression features of TS cells, possess the multipotency to differentiate into specialized trophoblast cell types, and can chimerize E13.5 and term placentas. We also demonstrate the capability of the haTSCs to undergo genetic manipulation and facilitate genome-wide screening in the trophoblast lineage. We expect that haTSCs will offer a powerful tool for studying functional genomics and placental biology.
滋养层干细胞（TS）细胞越来越多地被用作研究胎盘形成和胎盘疾病的模型系统。然而，遗传操作的实际限制给使用 TS 细胞进行遗传分析带来了挑战。在这里，我们报告了小鼠孤雌单倍体 TS 细胞（haTSC）的产生，并表明补充 FGF4 和抑制 Rho 相关蛋白激酶（ROCK）可维持其单倍体和发育潜能。所得的 haTSC 有 20 条染色体，表现出 TS 细胞的典型表达特征，具有分化为特化滋养层细胞类型的多能性，并能嵌合 E13.5 和足月胎盘。我们还证明了 haTSC 进行遗传操作的能力，并促进了滋养层谱系中的全基因组筛选。我们预计 haTSC 将为研究功能基因组学和胎盘生物学提供有力工具。
