Gene expression profile at single cell level of hepatocytes from hepatocyte derived liver organoid

In this study, we explored the effects of RNA splicing on hepatocyte fate decision. We found spatial remodeling of hepatic lobule during liver regeneration by spatial transcriptome analysis in regenerative and control mouse model. We also reported cell heterogeneity of hepatocyte-organoids and found that splicing factors reprogram hepatocytes from single-cell resolution. To explore the detailed function of splicing factors, splicing inhibitors (Pladienolide B) were used to treated organoids, then total RNA were harvest for bulk RNA sequence. In summary, we found that splicing factors can promote the transformation of hepatocytes from metabolic state to proliferative state by spatial transcriptome, single-cell RNA sequencing, and bulk RNA sequencing. Overall design: Mouse hepatocytes were obtained by two-step collagenase perfusion and culture into hepatocyte-organoids for 6 days. We performed single cell RNA sequencing of organoids for exploring detailed cell heterogeneity of hepatocytes of organoids.