Multi-zonal liver organoids from human pluripotent stem cells.

ABSTRACT: Distinct hepatocyte subpopulations are spatially segregated along the portal-central axis and are critical to understanding metabolic homeostasis and injury in the liver¹. Although several bioactive molecules, including ascorbate and bilirubin, have been described as having a role in directing zonal fates, zonal liver architecture has not yet been replicated in vitro^2,3. Here, to evaluate hepatic zonal polarity, we developed a self-assembling zone-specific liver organoid by co-culturing ascorbate- and bilirubin-enriched hepatic progenitors derived from human induced pluripotent stem cells. We found that preconditioned hepatocyte-like cells exhibited zone-specific functions associated with the urea cycle, glutathione synthesis and glutamate synthesis. Single-nucleus RN

SUBMITTER: Reza HA 

PROVIDER: S-EPMC12488051 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature