Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

作者：Jue Zhang, Li‐Fang Chu, Zhonggang Hou, Michael P. Schwartz, Timothy A. Hacker, Vernella Vickerman, Scott Swanson, Ning Leng, Bao Kim Nguyen, Angela L. Elwell, Jennifer M. Bolin, Matthew E. Brown, Ron Stewart, William J. Burlingham, William L. Murphy, James A. Thomson · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1702295114 · 被引用次数：145 · 研究领域：Single-cell and spatial transcriptomics、Angiogenesis and VEGF in Cancer、Congenital heart defects research

Significance Generating fully functional arterial endothelial cells is a critical problem for vascular development and disease research. Currently, the arterial endothelial cells derived from human pluripotent stem cells lack the range of arterial-specific functions in vitro and the protective function for ischemic tissues in vivo. Here, we combine single-cell RNA sequencing and CRISPR-Cas9 technology to identify pathways for regulating arterial endothelial cell differentiation. We then manipulate these pathways and generate arterial endothelial cells that demonstrate unprecedented arterial-specific functions as well as improve survival of myocardial infarction. These findings facilitate the understanding of vascular development and disease and provide a source of cells that have broad applications for vascular disease modeling and regenerative medicine.