Overview

• Only 15–20% of hepatocytes in newborn mice clonally expand to generate more than 90% of the adult liver mass.
• Homology-directed repair editing is enriched in these clonogenic cells, increasing the edited liver area as the organ grows.
• Lentiviral delivery becomes less permissive after weaning with the rise of peri-central identity and proteasome activity, but pretreatment with a proteasome inhibitor restored adult hepatocyte transduction.
• Single-cell and spatial transcriptomics, clonal tracing, and mathematical modeling mapped the cells’ molecular identities and a neonatal niche adjacent to hematopoietic progenitors.
• The Journal of Hepatology study from SR‑Tiget and collaborators outlines preclinical principles for timing, vector choice, and adjunct pharmacology, with ERC-backed follow-up work planned.