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Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury [Rspo3 KO]

ABSTRACT: We find that lymphatic Rspo3 is essential for intestinal regeneration after cytotoxic injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE198465 | GEO | 2022/07/18

REPOSITORIES: GEO

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Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury [endothelial cells]

Project description:We find that lymphatic Rspo3 is essential for intestinal regeneration after cytotoxic injury.

2022-07-18 | GSE198468 | GEO

Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury [Rspo3 KO]

Project description:Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury [Rspo3 KO]

| PRJNA815348 | ENA

Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

Project description:Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

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Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-18 | GSE198469 | GEO

Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury [endothelial cells]

Project description:Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury [endothelial cells]

| PRJNA815355 | ENA

Lymphatic endothelial cells, together with Rspo3+Grem1+ fibroblasts, support intestinal stem cells through the production of R-spondin3 in homeostasis and injury [scRNAseq]

Project description:Intestinal stem cells (ISCs) depend on niche factors for proper function. Here, we focus on RSPO3, an essential ISC niche factor, that engages the Lgr5 receptor on ISCs to potentiate WNT signaling, an interaction that is critical for maintaining intestinal stemness. Leveraging novel Rspo3-GFP and Grem1-tdTomato-CreERT2 genetically engineered mice together with single-cell mRNA profiling, we find that RSPO3 is expressed by lymphatic endothelial cells (LECs) and Rspo3+Grem1+ (RG) fibroblasts in the intestinal stroma where RG fibroblasts surround lymphatics and are in close proximity to Lgr5+ ISCs near the crypt base. Functionally, RG fibroblasts through the production of RSPO3 and GREM1 and LECs through the production of RSPO3 foster intestinal organoid propagation in vitro. Rspo3 loss in either or both of these niche cells in vivo compromises ISC numbers, villi length, and repair after irradiation-induced injury. Mechanistically, irradiation-induced damage expands LEC and RG fibroblast numbers and enhances the latters’ generation of RSPO3 through IL-1 receptor activation. We propose that LECs represent a novel component of the ISC niche, which together with RG fibroblasts, provide essential RSPO3 to sustain ISCs in homeostasis and regeneration.

2022-09-08 | GSE185354 | GEO

Lymphatic endothelial cells, together with Rspo3+Grem1+ fibroblasts, support intestinal stem cells through the production of R-spondin3 in homeostasis and injury [200909Yil]

2022-09-08 | GSE185350 | GEO

Lymphatic endothelial cells, together with Rspo3+Grem1+ fibroblasts, support intestinal stem cells through the production of R-spondin3 in homeostasis and injury [200211YilA]

2022-09-08 | GSE185348 | GEO

Targeting PTPRK-RSPO3 tumors

Project description:Targeting PTPRK-RSPO3 colon tumors.

| PRJEB10684 | ENA

Identification of endothelial genes co-regulated upon endothelial Evi/Wls and Rspo3 deletion

Project description:Inducible endothelial Rspo3 deletion resulted in perturbed developmental and tumor vascular remodeling. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified novel target genes, which could be linked to WNT/Ca2+/NFAT signaling. In summary, the study identifies endothelial RSPO3-driven non canonical WNT/Ca2+/NFAT signaling as critical maintenance pathway of the remodeling vasculature.

2016-02-03 | GSE75836 | GEO

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