hPSC-derived Venous Angioblasts Generate Mature Fenestrated LSECs Following Intrahepatic Transplantation

The vasculature of the liver is highly specialized and critical to organ function as well as future efforts to engineer new liver tissue. One key vascular sub type, the liver sinusoidal endothelial cell (LSEC) lines the hepatic sinusoid mediating functions such as passing nutrients to hepatocytes, scavenging blood components, secreting FVIII, and mediating regeneration. To better understand human LSECs and to generate them from human pluripotent stem cells, we differentiated hPSCs to venous endothelial progenitors known as angioblasts, transplanted them intrahepatically in NSG newborn mice, waited 77-days, and isolated the hPSC-derived cells (DAPI-, tdRFP+) for scRNA-seq. This scRNA-seq sample represents a large number of hPSC-derived, matured hepatic- origin fibroblast and endothelial cell types. Providing a high resolution, large sample population of cells that correlate closely to MacParland et al. (2018, Nat. Commun.) hepatic endothelial clusters providing increased cell population resolution sufficient for human LSEC zonation assessment in a tractable transplantation system. Overall design: Primary FACS cleaned hPSC-derived hepatic engraftment population from Day 8 venous angioblast population at 77-days post transplant