@article{75c5afaa28e74cc598002140a3d7969a,
title = "Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome",
abstract = "Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here, we demonstrate that naive hESCs can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting “transdifferentiated” hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results suggest that naive hESCs can differentiate to extra-embryonic lineage and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.",
keywords = "DNA methylation, amnion, development, differentiation, embryonic stem cells, epigenetics, placenta, pluripotency, trophoblast",
author = "Cinkornpumin, {Jessica K.} and Kwon, {Sin Young} and Yixin Guo and Ishtiaque Hossain and Jacinthe Sirois and Russett, {Colleen S.} and Tseng, {Hsin Wei} and Hiroaki Okae and Takahiro Arima and Duchaine, {Thomas F.} and Wanlu Liu and Pastor, {William A.}",
note = "Funding Information: We thank the Goodman Cancer Research Center Flow Cytometry core, the SickKids Center for Applied Genomics Facility, the La Jolla Institute for Allergy and Immunology Sequencing Core, and the Canada Michael Smith Genome Sciences Center at BC Cancer for their dedicated service. We thank the Rudolph Jaenisch (MIT) and Thorold Theunissen (Washington University) labs for providing WIBR3 OCT4-ΔPE-GFP hESCs, and the Amander Clark lab (UCLA) for providing UCLA1 hESCs. This work was funded by the New Frontiers in Research Fund (NFRF) grant NFRFE-2018-00883 and the Canadian Institutes of Health Research (CIHR) project grant PJT-166169 to W.A.P., the Zhejiang Provincial Natural Science Foundation of China , LQ20C060004 to W.L., and PJT-165996 to T.F.D. J.K.C. was supported by a Fonds de recherche Sant{\'e} Qu{\'e}bec graduate fellowship. J.K.C. and I.H. were supported by studentships from the McGill University Faculty of Medicine . Funding Information: We thank the Goodman Cancer Research Center Flow Cytometry core, the SickKids Center for Applied Genomics Facility, the La Jolla Institute for Allergy and Immunology Sequencing Core, and the Canada Michael Smith Genome Sciences Center at BC Cancer for their dedicated service. We thank the Rudolph Jaenisch (MIT) and Thorold Theunissen (Washington University) labs for providing WIBR3 OCT4-?PE-GFP hESCs, and the Amander Clark lab (UCLA) for providing UCLA1 hESCs. This work was funded by the New Frontiers in Research Fund (NFRF) grant NFRFE-2018-00883 and the Canadian Institutes of Health Research (CIHR) project grant PJT-166169 to W.A.P. the Zhejiang Provincial Natural Science Foundation of China, LQ20C060004 to W.L. and PJT-165996 to T.F.D. J.K.C. was supported by a Fonds de recherche Sant? Qu?bec graduate fellowship. J.K.C. and I.H. were supported by studentships from the McGill University Faculty of Medicine. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = jul,
day = "14",
doi = "10.1016/j.stemcr.2020.06.003",
language = "English",
volume = "15",
pages = "198--213",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "1",
}