气候变化领域集成服务门户(CCPortal): Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate

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DOI	10.1073/pnas.2016950118
	Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate
	Lu T.M.; Houghton S.; Magdeldin T.; Barcia Durán J.G.; Minotti A.P.; Snead A.; Sproul A.; Nguyen D.-H.T.; Xiang J.; Fine H.A.; Rosenwaks Z.; Studer L.; Rafii S.; Agalliu D.; Redmond D.; Lis R.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Cells derived from pluripotent sources in vitro must resemble those found in vivo as closely as possible at both transcriptional and functional levels in order to be a useful tool for studying diseases and developing therapeutics. Recently, differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cells (ECs) with blood–brain barrier (BBB)-like properties has been reported. These cells have since been used as a robust in vitro BBB model for drug delivery and mechanistic understanding of neurological diseases. However, the precise cellular identity of these induced brain microvascular endothelial cells (iBMECs) has not been well described. Employing a comprehensive transcriptomic metaanalysis of previously published hPSC-derived cells validated by physiological assays, we demonstrate that iBMECs lack functional attributes of ECs since they are deficient in vascular lineage genes while expressing clusters of genes related to the neuroectodermal epithelial lineage (Epi-iBMEC). Overexpression of key endothelial ETS transcription factors (ETV2, ERG, and FLI1) reprograms Epi-iBMECs into authentic endothelial cells that are congruent with bona fide endothelium at both transcriptomic as well as some functional levels. This approach could eventually be used to develop a robust human BBB model in vitro that resembles the human brain EC in vivo for functional studies and drug discovery. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Blood–brain barrier; Cellular identity; Endothelial cells; Induced pluripotent; Single-cell RNA sequencing
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180565
作者单位	Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, United States; Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10065, United States; Department of Neurology, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY 10065, United States; Developmental Biology, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Biochemistry, Structural Biology, Cell Biology, Developmental Biology and Molecular Biology Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, United States; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, United States; Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY 10032, United...
推荐引用方式 GB/T 7714	Lu T.M.,Houghton S.,Magdeldin T.,et al. Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate[J],2021,118(8).
APA	Lu T.M..,Houghton S..,Magdeldin T..,Barcia Durán J.G..,Minotti A.P..,...&Lis R..(2021).Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Lu T.M.,et al."Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).