TY - JOUR
T1 - Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells
AU - Castel, Gaël
AU - Meistermann, Dimitri
AU - Bretin, Betty
AU - Firmin, Julie
AU - Blin, Justine
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
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/11/24
Y1 - 2020/11/24
N2 - 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.
AB - 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.
KW - OSKM
KW - cell fate conversion
KW - extended pluripotent stem cells
KW - human induced trophoblast stem cells
KW - human peri-implantation embryo
KW - human placenta
KW - induced pluripotent stem cells
KW - naive pluripotent stem cells
KW - somatic cell reprogramming
KW - trophoblast stem cells
UR - http://www.scopus.com/inward/record.url?scp=85096616959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096616959&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2020.108419
DO - 10.1016/j.celrep.2020.108419
M3 - Article
C2 - 33238118
AN - SCOPUS:85096616959
VL - 33
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 8
M1 - 108419
ER -