Direct conversion of human endothelial cells to hepatic progenitor cells
Abstract This protocol describes direct lineage reprogramming of human endothelial cells isolated from the umbilical vein and peripheral blood into hepatic progenitor cells. These induced human hepatic progenitor cells (hiHepPCs) proliferate in long-term culture and give rise to hepatocytes and cholangiocytes as descendants. To induce hiHepPCs from endothelial cells, we first established an efficient culture condition, enabling hiHepPC generation and propagation in a monolayer culture. Then, we confirmed the ability of the hiHepPCs to differentiate into mature hepatocytes by formation of cell aggregates in each well of ultra-low attachment 96-well plates. Furthermore, upon culturing in Matrigel, the hiHepPCs differentiated into cholangiocytes and formed cystic epithelial spheroids, similar to human liver-derived cholangiocytes. Direct induction of the expandable and bipotential human hepatic progenitor cells provides a possibility for generating cells such as hepatocytes and cholangiocytes, which will be useful for developing therapeutic strategies for human liver diseases.