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. Overall design: mRNA profiles of sorted ISC/progenitor cells from VSG vs. sham-treated dietary-induced obese mice.