Study of the effects of RNA splicing inhibitor Pladienolide B on hepatocyte proliferation in vitro
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: To investigate function of RNA splicing  in regulating hepatocytes fate determination,  Pladienolide B and DMSO were used to treat hepatocyte-organoid. We then performed gene expression profiling analysis using data obtained from RNA-seq of 6 different samples containing 3 DMSO treated and 3 Pladienolide B treated.