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Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression.

ABSTRACT: Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression.

PROVIDER: PRJNA1169100 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30890700_1.fastq.gz	Fastqsanger.gz
	SRR30890700_2.fastq.gz	Fastqsanger.gz
	SRR30890701_1.fastq.gz	Fastqsanger.gz
	SRR30890701_2.fastq.gz	Fastqsanger.gz
	SRR30890702_1.fastq.gz	Fastqsanger.gz

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Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression.

Project description:Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor evolution. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. Here we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify loss of stromal KITL during tumorigenesis as tumor-promoting. Genetic inhibition of mesenchymal KITL in the contexts of homeostasis, injury, and cancer together indicate a role for KITL signaling in maintenance of pancreas tissue architecture, such that loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment.

2024-10-14 | GSE278857 | GEO

RNA-Seq of PreCFU-E and CFU-E progenitors from wild type and Scf mutants

Project description:It has been shown previously that endothelial cells and LepR+ stromal cells are the main sources of SCF in vivo in the mouse bone marrow. We tested whether SCF from endothelial cells and/or LepR+ stromal cells is important for the maintenance of hematopoietic progenitors and erythroid progenitors in mouse bone marrow by conditional deletion of Scf from these two cell types. We discovered that Scf deletion from LepR+ stromal cells, but not endothelial cells, reduced the numbers of hematopoietic progenitors and erythroid progenitors in mice. We performed RNA-Seq on PreCFU-E and CFU-E progenitors from control mice and from mice with Scf deletion from LepR+ stromal cells. We discovered that lack of SCF from LepR+ cells induces a premature differentiation of PreCFU-E and CFU-E progenitors.

2018-12-09 | GSE122468 | GEO

SWI/SNF component ARID1A restrains pancreatic neoplasia formation [ChIP-seq]

Project description:ARID1A restrains the formation of PanIN, pancreas ductal adenocarcinoma, and intraductal mucinous neoplasms

2018-09-12 | GSE119858 | GEO

SWI/SNF component ARID1A restrains pancreatic neoplasia formation [RNA-seq]

Project description:ARID1A restrains the formation of PanIN, pancreas ductal adenocarcinoma, and intraductal mucinous neoplasms

2018-09-12 | GSE119779 | GEO

Stromal-derived NRG1 enables oncogenic KRAS bypass in pancreas cancer

Project description:Stromal-derived NRG1 enables oncogenic KRAS bypass in pancreas cancer

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CD54+BP1+YFP- bone marrow stromal cells from IL7 reporter mice

Project description:Hematopoiesis in adult mammals involves cognate interactions between developing hematopoietic cells and bone marrow stromal cell niches. SCF and CXCL12 play key roles in the maintenance of HSC, while early B cell differentiation requires CXCL12 and IL7. In this study, we characterized mouse BM stromal cells expressing IL7 by performing a transcriptomic analysis. We found that SCF, CXCL12 and IL7 were co-expressed by a unique peri-sinusoidal stromal cell subset.

2019-03-01 | GSE90584 | GEO

A Novel Approach for Pancreas Transcriptomics Reveals the Cellular Landscape in Homeostasis and Acute Pancreatitis

Project description:BACKGROUND & AIMS: Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing (scRNA-seq) studies of the pancreas underrepresent acinar cells relative to histological expectations, and a robust approach to capture pancreatic cell responses in disease states is needed. We sought to innovate a method that overcomes these challenges to accelerate study of the pancreas in health and disease. METHODS: We introduce FixNCut, a scRNA-seq approach where tissue is reversibly fixed with dithiobis(succinimidyl propionate) prior to dissociation and single-cell preparation. We apply FixNCut to an established mouse model of acute pancreatitis, validate findings using GeoMx whole transcriptome atlas (WTA) profiling, and integrate our data with prior studies to benchmark our method in both mouse and human pancreas datasets. RESULTS: FixNCut achieves unprecedented definition of challenging pancreatic cells including acinar and immune populations in homeostasis and acute pancreatitis, and identifies changes in all major cell types during injury and recovery. We define the acinar transcriptome during homeostasis and acinar-to-ductal metaplasia and establish a unique gene set to measure deviation from normal acinar identity. We characterize pancreatic immune cells, and analysis of T-cell subsets reveals a polarization of the homeostatic pancreas towards type-2 immunity. We report immune responses during acute pancreatitis and recovery, including early neutrophil infiltration, expansion of dendritic cell subsets, and a substantial shift in the transcriptome of macrophages due to both resident macrophage activation and monocyte infiltration. CONCLUSIONS: FixNCut preserves pancreatic transcriptomes to uncover novel cell states during homeostasis and following pancreatitis, establishing a broadly applicable approach and reference atlas for study of pancreas biology and disease.

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Gene expression of glucose homeostasis in a pancreas-liver microphysiological system

Project description:Gene expression of glucose homeostasis in a pancreas-liver microphysiological system

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Scf-GFP+ cells from the bone marrow and whole bone marrow microarray

Project description:The HSC niche factor SCF is required for HSC maintenance. Using an Scf-GFP knockin mouse, we have identified a perivascular cell type in the bone marrow expressing high level of Scf. To characterize the novel Scf-GFP+ cells from the bone marrow, we performed microarray analysis on these cells.

2012-02-01 | GSE33158 | GEO

Peri-sinusoidal stromal cells form a unique multispecific niche for hematopoietic stem cells and early B cells

Project description:In the bone marrow, CXCL12 and IL7 are essential for B cell differentiation whereas hematopoietic stem cells (HSC) maintenance requires SCF and CXCL12. Previous studies, including ours, indicate that peri-sinusoidal stromal (PSS) cells are heterogeneous and that part of them express and are the main source of IL7. Our single cell qPCR and transcriptomic analysis demonstrate that SCF, CXCL12 and IL7 are co-expressed by a unique peri-sinusoidal stromal cell subset.

2019-03-01 | GSE121568 | GEO

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