4.8 Article

Derivation of Mouse Haploid Trophoblast Stem Cells

Journal

CELL REPORTS
Volume 26, Issue 2, Pages 407-+

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2018.12.067

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Funding

  1. Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16030400]
  2. National Basic Research Program of China [2014CB964800]
  3. National Natural Science Foundation of China [31621004, 31422038]
  4. National Key Research and Development Program [2017YFA0103803]
  5. CAS Key Projects [QYZDY-SSW-SMC022, QYZDB-SSW-SMC002]

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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.

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