Fetal hepatocytes protect the HSPC genome via fetuin-A.

ABSTRACT: The maintenance of genomic integrity in rapidly proliferating cells is a substantial challenge during embryonic development^1-3. Although numerous cell-intrinsic mechanisms have been revealed^4-7, little is known about genome-protective effects and influences of developmental tissue microenvironments on tissue-forming cells. Here we show that fetal liver hepatocytes provide protection to haematopoietic stem and progenitor cell (HSPC) genomes. Lineage tracing and depletion in mice demonstrated that delayed hepatocyte development in early fetal livers increased the chromosomal instability of newly colonizing HSPCs. In addition, HSPCs developed tolerance to genotoxins in hepatocyte-conditioned medium, suggesting that hepatocytes protect the HSPC genome in a paracrine manne

SUBMITTER: Guo XL 

PROVIDER: S-EPMC11711094 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature