Derivation of Mouse Haploid Trophoblast Stem Cells

Cell Rep. 2019 Jan 8;26(2):407-414.e5. doi: 10.1016/j.celrep.2018.12.067.

Abstract

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.

Keywords: TSC; haploidy; stem cells; trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Female
  • Fibroblast Growth Factor 4 / pharmacology
  • Haploidy*
  • Karyotype
  • Mice
  • Primary Cell Culture / methods
  • Trophoblasts / cytology*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism

Substances

  • Fibroblast Growth Factor 4
  • rho-Associated Kinases