Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome

Jessica K. Cinkornpumin, Sin Young Kwon, Yixin Guo, Ishtiaque Hossain, Jacinthe Sirois, Colleen S. Russett, Hsin Wei Tseng, Hiroaki Okae, Takahiro Arima, Thomas F. Duchaine, Wanlu Liu, William A. Pastor

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here, we demonstrate that naive hESCs can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting “transdifferentiated” hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results suggest that naive hESCs can differentiate to extra-embryonic lineage and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.

Original languageEnglish
Pages (from-to)198-213
Number of pages16
JournalStem Cell Reports
Volume15
Issue number1
DOIs
Publication statusPublished - 2020 Jul 14

Keywords

  • DNA methylation
  • amnion
  • development
  • differentiation
  • embryonic stem cells
  • epigenetics
  • placenta
  • pluripotency
  • trophoblast

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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