Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells

Gaël Castel, Dimitri Meistermann, Betty Bretin, Julie Firmin, Justine Blin, Sophie Loubersac, Alexandre Bruneau, Simon Chevolleau, Stéphanie Kilens, Caroline Chariau, Anne Gaignerie, Quentin Francheteau, Harunobu Kagawa, Eric Charpentier, Léa Flippe, Valentin François--Campion, Sandra Haider, Bianca Dietrich, Martin Knöfler, Takahiro ArimaJérémie Bourdon, Nicolas Rivron, Damien Masson, Thierry Fournier, Hiroaki Okae, Thomas Fréour, Laurent David

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access to human embryos and first-trimester placentas is limited, thus preventing the establishment of hTSCs from diverse genetic backgrounds associated with placental disorders. Here, we show that hTSCs can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (1) somatic cell reprogramming of adult fibroblasts with OCT4, SOX2, KLF4, MYC (OSKM) and (2) cell fate conversion of naive and extended pluripotent stem cells. The resulting induced/converted hTSCs recapitulated hallmarks of hTSCs including long-term self-renewal, expression of specific transcription factors, transcriptomic signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSCs and show that these cells resemble day 8 cytotrophoblasts. Altogether, hTSC lines of diverse genetic origins open the possibility to model both placental development and diseases in a dish.

Original languageEnglish
Article number108419
JournalCell Reports
Volume33
Issue number8
DOIs
Publication statusPublished - 2020 Nov 24
Externally publishedYes

Keywords

  • OSKM
  • cell fate conversion
  • extended pluripotent stem cells
  • human induced trophoblast stem cells
  • human peri-implantation embryo
  • human placenta
  • induced pluripotent stem cells
  • naive pluripotent stem cells
  • somatic cell reprogramming
  • trophoblast stem cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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