BioProject

Cholestatic injuries, featured with regional damage around the periportal, cause considerable mortality without curative therapies. More...

Cholestatic injuries, featured with regional damage around the periportal, cause considerable mortality without curative therapies. It is technically challenging to dissect regional cell-cell interactions and molecular changes to fully understand cholangiopathies. Here, we generated a high-definition atlas of spatiotemporal transcriptome during cholestatic injury and repair. Remarkably, cholangiocytes functioned as a periportal hub by integrating signals from neighboring cells. We also dissected periportal damage, spatial heterogenous reprogramming and zonal regeneration, which appeared to be strongly associated with cholangiocyte. Moreover, spatiotemporal analyses revealed a key inhibitory rheostat for hepatocyte proliferation. Together, our study provides a comprehensive resource that is instrumental to demarcate regional cholestatic injury. Overall design: Comparative gene expression profiling analysis of RNA-seq data for resting hepatocytes (shNC) and its knockdown derivatives (shAtoh8) after DDC diet for 17 days. Less...