title: Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells.
abstract: Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C-MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single-cell gene expression signatures of human iPSC-derived ECs. We derived human iPSCs from 3 types of somatic cells of the same individuals: fibroblasts (FB-iPSCs), ECs (EC-iPSCs), and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into ECs by sequential administration of Activin, BMP4, bFGF, and VEGF. EC-iPSCs at early passage (10 < P < 20) showed higher EC differentiation propensity and gene expression of EC-specific markers (PECAM1 and NOS3) than FB-iPSCs and CPC-iPSCs. In vivo transplanted EC-iPSC-ECs were recovered with a higher percentage of CD31+population and expressed higher EC-specific gene expression markers (PECAM1, KDR, and ICAM) as revealed by microfluidic single-cell quantitative PCR (qPCR). In vitro EC-iPSC-ECs maintained a higher CD31+population than FB-iPSC-ECs and CPC-iPSC-ECs with long-term culturing and passaging. These results indicate that cellular origin may influence lineage differentiation propensity of human iPSCs; hence, the somatic memory carried by early passage iPSCs should be carefully considered before clinical translation.
authors.affiliation: Stanford Cardiovascular Institute.|Department of Medicine, Division of Cardiology, and.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.|Institute for Cardiovascular Science, Soochow University & Department of Cardiovascular Surgery of the First Affiliated Hospital, Suzhou, Jiangsu, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: Stanford Cardiovascular Institute.|Department of Medicine, Division of Cardiology, and.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ming-Tao
authors.initials: MT
authors.lastname: Zhao
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Jahanbani
authors.affiliation: Stanford Cardiovascular Institute.|Department of Medicine, Division of Cardiology, and.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ning-Yi
authors.initials: NY
authors.lastname: Shao
authors.affiliation: Stanford Cardiovascular Institute.|Department of Medicine, Division of Cardiology, and.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Stanford Cardiovascular Institute.|Department of Medicine, Division of Cardiology, and.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Haodong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
authors.affiliation: Stanford Cardiovascular Institute.|Department of Medicine, Division of Cardiology, and.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D042783:Endothelial Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology*; D000066449:Human Embryonic Stem Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D009206:Myocardium / Q000166:cytology*