GSE135362
Compared gene expression profile of Lgr5-expressing and deficient stem cells in the intestine
The Lgr5 receptor is a marker of intestinal stem cells (ISCs) that regulates Wnt/b-catenin signaling. In this study, phenotype analysis of knockin/knockout Lgr5-eGFP-IRES-Cre and Lgr5-DTReGFP embryos revealed that Lgr5 deficiency during Wnt-mediated cytodifferentiation results in amplification of ISCs and early differentiation into Paneth cells, which can be counteracted by in utero treatment with the Wnt inhibitor LGK974. Conditional ablation of Lgr5 postnatally, but not in adults, altered stem cell fate towards the Paneth lineage. Together, these in vivo studies suggest that Lgr5 is part of a feedback loop to adjust the Wnt tone in ISCs. Moreover, transcriptome analyses revealed that Lgr5 controls fetal ISC maturation associated with acquisition of a definitive stable epithelial phenotype, that depends on the capacity of ISCs to generate their own extracellular matrix. Finally, using the ex vivo culture system, evidences are provided that Lgr5/Rspondin 2 interaction negatively regulates the pool of ISCs in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISC. Overall design: mRNA profiles of knockin/knockout Lgr5-eGFP-IRES-Cre and Lgr5-DTReGFP embryos versus heterozygous ISC at embryonic and adult stage.