Chemical reprogramming of mouse embryonic and adult fibroblast into endoderm lineage

We report here an approach to redirect somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts (MEFs) to epithelial-like cells (ciELC) with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting ELCs that can be further reprogrammed to endodermal progenitor cells (ciEPC). Interestingly, these cells can self-renew in vitro and further differentiate into albumin-producing hepatocytes that can rescue mice from acute live injury. Our results demonstrate a rational approach to convert MEFs to hepatocytes and suggest that this mechanism-driven approach may be generalized for other cells. Overall design: Examination of mouse fibroblasts, ciEPCs, ciHeps, ESC derived EPCs and primary hepatocytes