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JCI Insight. 2016 Jun 2;1(8). pii: e85558.

Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells.

Author information

1
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California, USA.; 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.
2
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
3
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

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.

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