1. Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells
- Author
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Castel, Gaël, Meistermann, Dimitri, Bretin, Betty, Firmin, Julie, Blin, Justine, Loubersac, Sophie, Bruneau, Alexandre, Chevolleau, Simon, Kilens, Stéphanie, Chariau, Caroline, Gaignerie, Anne, Francheteau, Quentin, Kagawa, Harunobu, Charpentier, Eric, Flippe, Léa, François--Campion, Valentin, Haider, Sandra, Dietrich, Bianca, Knöfler, Martin, Arima, Takahiro, Bourdon, Jérémie, Rivron, Nicolas, Masson, Damien, Fournier, Thierry, Okae, Hiroaki, Fréour, Thomas, David, Laurent, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Austrian Academy of Sciences (OeAW), Medizinische Universität Wien = Medical University of Vienna, Tohoku University [Sendai], and The Enteric Nervous System in gut and brain disorders [U1235] (TENS)
- Subjects
Pluripotent Stem Cells ,human induced trophoblast stem cells ,induced pluripotent stem cells ,[SDV]Life Sciences [q-bio] ,naive pluripotent stem cells ,Cell Differentiation ,somatic cell reprogramming ,Trophoblasts ,cell fate conversion ,[SDV] Life Sciences [q-bio] ,human placenta ,Pregnancy ,embryonic structures ,Humans ,OSKM ,Female ,extended pluripotent stem cells ,trophoblast stem cells ,human peri-implantation embryo ,reproductive and urinary physiology - Abstract
International audience; 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.
- Published
- 2020
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