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 Arima; Jérémie Bourdon; Nicolas Rivron; Damien Masson; Thierry Fournier; Hiroaki Okae; Thomas Fréour; Laurent David

doi:10.1016/j.celrep.2020.108419

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

Medicine (department affiliation only)

Research output: Contribution to journal › Article › peer-review

47 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 language	English
Article number	108419
Journal	Cell Reports
Volume	33
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2020.108419
Publication status	Published - 2020 Nov 24

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)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2020.108419

Cite this

Castel, G., Meistermann, D., Bretin, B., Firmin, J., Blin, J., Loubersac, S., Bruneau, A., Chevolleau, S., Kilens, S., Chariau, C., Gaignerie, A., Francheteau, Q., Kagawa, H., Charpentier, E., Flippe, L., François--Campion, V., Haider, S., Dietrich, B., Knöfler, M., ... David, L. (2020). Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells. Cell Reports, 33(8), [108419]. https://doi.org/10.1016/j.celrep.2020.108419

Castel, G, Meistermann, D, Bretin, B, Firmin, J, Blin, J, Loubersac, S, Bruneau, A, Chevolleau, S, Kilens, S, Chariau, C, Gaignerie, A, Francheteau, Q, Kagawa, H, Charpentier, E, Flippe, L, François--Campion, V, Haider, S, Dietrich, B, Knöfler, M, Arima, T, Bourdon, J, Rivron, N, Masson, D, Fournier, T, Okae, H, Fréour, T & David, L 2020, 'Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells', Cell Reports, vol. 33, no. 8, 108419. https://doi.org/10.1016/j.celrep.2020.108419

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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.",

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AU - Loubersac, Sophie

AU - Bruneau, Alexandre

AU - Chevolleau, Simon

AU - Kilens, Stéphanie

AU - Chariau, Caroline

AU - Gaignerie, Anne

AU - Francheteau, Quentin

AU - Kagawa, Harunobu

AU - Charpentier, Eric

AU - Flippe, Léa

AU - François--Campion, Valentin

AU - Haider, Sandra

AU - Dietrich, Bianca

AU - Knöfler, Martin

AU - Arima, Takahiro

AU - Bourdon, Jérémie

AU - Rivron, Nicolas

AU - Masson, Damien

AU - Fournier, Thierry

AU - Okae, Hiroaki

AU - Fréour, Thomas

AU - David, Laurent

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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