Transplantation-induced progenitor-like state determines successful hepatocyte engraftment

Here, we identified a conserved reprogramming state of Tx-Heps during engraftment, marked by the activation of liver progenitor genes and bipotential differentiation capacity.

Associated with enhanced fitness, transplantation reprogramming of Tx-Heps is crucial for successful engraftment, as proven by transplantation failure upon hepatocyte-specific ablation of Arid1a, which is essential for Tx-Hep reprogramming. To validate translational potential, we artificially induced Tx-Hep reprogramming via either IL6 or IC7, a chimeric IL6 family protein, significantly enhancing engraftment of both murine and human hepatocytes.