| Experiment Id | GSE13337 | Name | Altered cell lineage differentiation in fetal LGR5-null mice |
| Experiment Type | transcription profiling by array | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2022-10-31 |
| description | The molecular mechanisms controlling stem cell renewal and lineage commitment are still poorly understood due to lack of reliable markers. In the adult small intestine, an example of high rate self-renewing tissue, four different epithelial cell lineages (enterocytes, Goblet, enteroendocrine and Paneth cells) are generated from a pool of stem cells localised at the bottom of the crypts of LieberkÃŒhn. Recently, the orphan Leucine-rich repeat G protein-coupled receptor 5 (GPR49), a target of Wnt signalling, has been proposed as a marker for such cells. We investigated the role of LGR5 during intestinal development by using LGR5 null/LacZ-NeoR knock-in mice. We show that LGR5 deficiency leads to premature Paneth cell differentiation. X-gal staining on E18.5 intestine revealed that LGR5 expression is restricted to a few cells clustered within the intervillus region known to contain progenitor cells. In LGR5-null mice, expression from the LGR5 promoter was found upregulated, suggesting a loss of negative feedback control. However, neither epithelial cell proliferation nor cell migration appeared significantly impaired by LGR5 deficiency. Finally, transcriptional profiling of ileal mutant mice suggests that LGR5 plays a role in regulating the Wnt and Notch signalling pathways controlling progenitor renewal and differentiation. Microarray analysis was performed on four independent pairs of KO/WT E18.5-E19 embryos generated by three independent LGR5+/- couples. Ileum labeled RNA were hybridized to MEEBO arrays containing on average 38784 mouse 70mer oligonucleotide probes (Stanford University, US). |
