SOX17/ETV2 Improves the Direct Reprogramming of Adult Fibroblasts to Endothelial Cells

In this study, we directly reprogram adult human dermal fibroblasts (NHDF) into reprogrammed ECs (rECs) by overexpressing SOX17 in conjunction with ETV2. The rECs are capable of emulating in vitro and in vivo EC functions better than cells reprogrammed with ETV2 alone, such as improved reprogramming efficiency, enriched in more EC genes, and form large blood vessels carrying blood from the host, and most importantly, start to express eNOS in vivo. From these results, we present an improved method to reprogram adult fibroblasts into functional ECs and posit ideas for the future that could potentially further improve the reprogramming process. Overall design: NHDF were transduced with an ETV2 lentivirus (ETV2-ECs) or both the ETV2 and SOX17 lentivirus (rECs) to observe the effects of SOX17 on the fibroblast to EC transdifferentiation process. Each sample has biological triplicates. NHDF served as a negative control, while HUVEC served as a positive control.