Pluto Bioinformatics

GSE65395: Compared gene expression profile of gastric and intestinal progenitors grown as spheroids in the ex vivo culture system

Bulk RNA sequencing

In adult stomach, Lgr5 is a marker of epithelial glandular stem cells that grow in the three dimensional ex vivo culture system as organoids. However, little is known about the markers that characterize fetal progenitors before cytodifferentiation and their potential involvement in regenerative processes in adults. Using the ex vivo culture system, we isolated epithelial progenitors from the fetal stomach. These cells generated stable undifferentiated immortal spheroids showing lower growth factor requirements as compared to the adult-type gastric Lgr5-expressing organoids. Although very similar in their gene expression profiles, cultured fetal gastric and intestinal spheroids differentially expressed Sox2/Cdx2 genes involved in regional pre-patterning. Accordingly, gastric but not intestinal spheroids, spontaneously converted into the cell lineages of the adult glandular stomach ex vivo. In vivo, the Trop2 marker enriched in the fetal gastric spheroids was transiently expressed in the gastric epithelium before cytodifferentiation while it remained barely detectable under glandular homeostasis in adults. However, upon specific ablation of the Lgr5 stem cell pool, highly proliferative Trop2-expressing cells rapidly emerged in the adult epithelium, qualifying Trop2 as a marker of Lgr5-independent gastric stem cells. Together, these data indicate that the Trop2 receptor identifies gastric fetal progenitors and adult stem/progenitor cells involved in regeneration of glandular stomach. SOURCE: Frederick Libert (flibert@ulb.ac.be) - C2-140 ULB