Spatial transcriptomics reveals spatial remodling of hepatic lobule during liver regeneration

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: Undamaged and injuried mouse liver tissues were used for spatial transcriptome analysis: undamaged (Und), 24 hours after hepatectomy (PHx24h), 48 hours after hepatectomy (PHx48H) and chornic carbon tetrachloride injuried (CCl4).