Transplantation-induced progenitor-like state determines successful hepatocyte engraftment

ABSTRACT: Demonstrating safety and short-term efficacy in treating liver diseases, hepatocyte-based therapy still faces the challenge of limited engraftment of transplanted hepatocytes (Tx-Heps) in clinical settings, akin to issues encountered in cell therapy in other solid tissues. 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. Our findings unveil early-stage cell fate reprogramming during transplantation and propose a promising strategy to augment hepatocyte engraftment, which might serve as an interesting framework to be studied in cell transplantation for other solid tissues.

ORGANISM(S): Mus musculus

PROVIDER: GSE275204 | GEO | 2026/08/18

REPOSITORIES: GEO