Generation of human induced trophoblast stem cells

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.; FRANCOIS - - CAMPION, V.; HAIDER, S.; DIETRICH, B.; KNOFLER, M.; ARIMA, T.; BOURDON, J.; RIVRON, N.; MASSON, D.; FOURNIER, T.; OKAE, H.; FREOUR, T.; DAVID, L.

doi:10.1101/2020.09.15.298257

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bioRxiv · 10.1101/2020.09.15.298257

Generation of human induced trophoblast stem cells

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Abstract

Human trophoblast stem cells (hTSC) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the human placenta. However, access to human embryos and first trimester placentas is limited thus preventing the establishment of hTSC from a variety of genetic backgrounds associated with placental disorders. In the present study, we show that hTSC can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (I) somatic cell reprogramming of adult fibroblasts using the Yamanaka factors, and (II) cell fate conversion of naive and extended pluripotent stem cells. The resulted induced and converted hTSC (hiTSC/hcTSC) recapitulated hallmarks of hTSC including long-term self-renewal, expression of specific transcription factors, transcriptome-side signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSC and show that these cells resemble post-implantation NR2F2+ cytotrophoblasts (day 8-10). Altogether, hTSC lines of diverse genetics origins open the possibility to model both placental development and diseases in a dish. HighlightsO_LIReprogramming of human somatic cells to induced hTSC with OSKM C_LIO_LIConversion of naive and extended hPSC to hTSC C_LIO_LIGenetic diversity of hTSC lines C_LIO_LIDevelopmental matching of hTSC in the peri-implantation human embryo C_LI

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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., FRANCOIS - - CAMPION, V., HAIDER, S., DIETRICH, B., KNOFLER, M., ARIMA, T., BOURDON, J., RIVRON, N., MASSON, D., FOURNIER, T., OKAE, H., FREOUR, T., DAVID, L.. 2020-09-15. Generation of human induced trophoblast stem cells. https://doi.org/10.1101/2020.09.15.298257

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