Gene regulatory networks in differentiation and direct reprogramming of hepatic cells

Abstract

Liver development proceeds by sequential steps during which gene regulatory networks (GRNs) determine differentiation and maturation of hepatic cells. Characterizing the architecture and dynamics of these networks is essential for understanding how cell fate decisions are made during development, and for recapitulating these processes during in vitro production of liver cells for toxicology studies, disease modelling and regenerative therapy. Here we review the GRNs that control key steps of liver development and lead to differentiation of hepatocytes and cholangiocytes in mammals. We focus on GRNs determining cell fate decisions and analyse subcircuitry motifs that may confer specific dynamic properties to the networks. Finally, we put our analysis in the perspective of recent attempts to directly reprogram cells to hepatocytes by forced expression of transcription factors.

Keywords: Cholangiocyte; Hepatic cell differentiation; Hepatoblast; Hepatocyte; Liver development; Network dynamics.