Dataset Information

CXCL12 produced from Foxl1high mesenchymal cells modulates epithelial cell metabolism and prevents intestinal neoplasia (RNA-Seq)

ABSTRACT: Several mesenchymal cell populations are involved in the maintenance and differentiation of intestinal stem cells (ISCs) by secreting Wnts, R-spondins, and bone morphogenetic proteins. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we revealed that CXCL12 produced from Foxl1high sub-epithelial mesenchymal cells regulates epithelial cell proliferation through modulation of the mevalonate pathway, which contributes to prevention of tumorigenesis. Foxl1-cre; Cxcl12f/f mice showed increase in the number of Ki67+ proliferative cells in the colonic epithelium, which was decreased by treatment with mevalonate biogenesis inhibitor simvastatin. Moreover, Cxcl12 deficiency in Foxl1high mesenchymal cells promoted adenoma development in the colon and ileum of ApcMin/+ mice. Collectively, these results demonstrate the critical role of CXCL12 derived from Foxl1high sub-epithelial cells in prevention of intestinal neoplasia through modulation of cellular metabolism in epithelial cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE254705 | GEO | 2025/01/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Hematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation, and trafficking. Endosteal osteoblasts and perivascular stromal cells including endothelial cells3, CXCL12-abundant reticular (CAR) cells, leptin-receptor positive stromal cells, and nestin-GFP positive mesenchymal progenitors have all been implicated in HSC maintenance. However, it is unclear if specific hematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (stromal-derived factor-1, SDF-1) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations. Here, we selectively deleted Cxcl12 from candidate niche stromal cell populations and characterized the effect on HPCs. Deletion of Cxcl12 from mineralizing osteoblasts has no effect on HSCs or lymphoid progenitors. Deletion of Cxcl12 from osterix-expressing stromal cells, which includes CAR cells and osteoblasts, results in constitutive HPC mobilization and a loss of B lymphoid progenitors, but HSC function is normal. Cxcl12 deletion in endothelial cells results in a modest loss of long-term repopulating activity. Strikingly, deletion of Cxcl12 in nestin-negative mesenchymal progenitors using Prx1-Cre is associated with a marked loss of HSCs, long-term repopulating activity, HSC quiescence, and common lymphoid progenitors. These data suggest that osterix-expressing stromal cells comprise a distinct niche that supports B lymphoid progenitors and retains HPC in the bone marrow, while expression of CXCL12 from stromal cells in the perivascular region, including endothelial cells and mesenchymal progenitors, support HSCs. Total of three samples of two groups analyzed. Replica samples of CXCL12-abundant reticular (CAR) cells from two CXCL12-GFP knock-in mice and a combined sample of PDGFRa+ Sca+ CD45- lineage- cells from three Prx1-Cre Rosa26Ai9/+ Cxcl12gfp/+ mice were used and analyzed.

Dataset Information

CXCL12 produced from Foxl1high mesenchymal cells modulates epithelial cell metabolism and prevents intestinal neoplasia (RNA-Seq)

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets