Acquisition of epithelial plasticity in human chronic liver disease

For many adult human organs,tissue regeneration during chronic disease remains a controversial subject.Regenerative processes are easily observed in animal models,and their underlying mechanisms are becoming well characterized1-4,but technical challenges and ethical aspects are limiting the validation of these results in humans.We decided to address this difficulty with respect to the liver.This organ displays the remarkable ability to regenerate after acute injury,although liver regeneration in the context of recurring injury remains to be fully demonstrated.Here we performed single-nucleus RNA sequencing(snRNA-seq)on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression.We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture.