Chemical reprogramming of mouse embryonic and adult fibroblast into endoderm lineage

Abstract We report here an approach to redirecting somatic cellfate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblaststo epithelial-like cells with chemicals and growth factors. Subsequent cell fate mappingreveals a robust induction of SOX17 in the resulting epithelial-like cells that can be further reprogrammedto endodermalprogenitor cells. Interestingly, these cells can self-renew in vitro and further differentiate into albumin-producing hepatocytes that can rescue mice from acute liver injury. Our results demonstrate a rational approach to convert mouse embryonic fibroblaststo hepatocytes and suggest that this mechanism-driven approach may be generalized for other cells.