Spatiotemporal liver dynamics shape hepatocellular heterogeneity and impact in vivo gene engineering.

ABSTRACT:

Background & aims

Hepatocytes are the liver's main functional cells and are key targets for in vivo gene therapy to treat monogenic diseases. Integrating the transgene into the genome is critical for long-term expression from a single early-life dose, which is achievable via integrating vectors or genome editing. To ensure persistence through liver growth and cell turnover, it is also necessary to target the hepatocytes driving these processes. While liver regeneration and homeostasis have been studied extensively, hepatocyte growth and maturation remain less well understood. Here, we investigate how hepatocyte heterogeneity evolves during liver growth and its implications for in vivo gene engineering.

Methods

We performed clonal tracing, as well as single-cell and spatial t

SUBMITTER: Milani M 

PROVIDER: S-EPMC12659782 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature