Transient ETV2 Expression Promotes the Generation of Mature Endothelial Cells from Human Pluripotent Stem Cells.

ABSTRACT

Differentiation protocols are used for induced pluripotent stem cells (iPSCs) in in vitro disease modeling and clinical applications. Transplantation of endothelial cells (ECs) is an important treatment strategy for ischemic diseases. For example, in vitro generated ECs can be used to provide the vascular plexus to regenerate organs such as the liver. Here, we demonstrate that the E-twenty-six (ETS) transcription factor ETV2 alone can directly convert iPSCs into vascular endothelial cells (iPS-ETV2-ECs) with an efficiency of over 90% within 5 d. Although the stable overexpression of ETV2 induced the expression of multiple key factors for endothelial development, the induced ECs were less mature. Furthermore, doxycycline-inducible transient ETV2 expression could upregulate the expression of von Willebrand factor (vWF) in iPS-ETV2-ECs, leading to a mature phenotype. The findings of this study on generation of mature iPS-ETV2-ECs provide further insights into the exploration of cell reprogramming from iPSCs. Here, we provide a new protocol for differentiation of iPSCs, thus providing a new source of ECs for in vitro disease modeling and clinical applications.