Gene expression profile chqnge of intestinal stem cells after VSG bariatric surgery

To investigate the effect of vertical sleeve gastrectomy (VSG) on intestinal stem cell (ISC)/progenitor cells, we performed VSG on a dietary-induced obese mouse models that expresses eGFP fluorescence tag in its Lgr5 gene, a specific marker of ISCs. We then performed RNAseq on the GFP-positive ISCs sorted from the duodenal, jejunal, and ileal epithelia. We pre-sorted immune cells (CD45 positive), endothelial cells (CD31 positive), apoptotic (Annexin5 positive), and dead cells (stained with Sytox blue). By performing differential expression analysis (P < 0.05, adjusted P <0.2, log2 fold change > 0.5, normalized count > 50 by DESeq2), we found that VSG altered 467 genes (259 up; 208 down) in the duodenum, 510 genes (348 up; 162 down) in the jejunum, and 955 genes (600 up; 355 down) in the ileum. Of note, some of the VSG-increased genes are region-specific. Overall, our data suggest that VSG induces ISC fate toward enteroendocrine cell differentiation and that there are critical regional differences among ISCs in the duodenum, jejunum, and ileum. mRNA profiles of sorted ISC/progenitor cells from VSG vs. sham-treated dietary-induced obese mice.