Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mus musculus

ABSTRACT: CXCL12/CXCR4 signaling mediates niche occupancy and tumor maintenance in T-cell leukemia

PROVIDER: PRJNA258103 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR1548450.fastq.gz	Fastqsanger.gz
	SRR1548451.fastq.gz	Fastqsanger.gz
	SRR1548452.fastq.gz	Fastqsanger.gz
	SRR1548453.fastq.gz	Fastqsanger.gz
	SRR1548444.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

The bone marrow niche regulates redox and energy balance in leukemia stem cells

Project description:The Cxcr4-Cxcl12 axis has been postulated as a critical pathway dictating leukemia stem cell (LSCs) chemoresistance in AML due to its role in controlling cellular egress from the marrow. Nevertheless, the cellular source of Cxcl12 in the AML microenvironment and the mechanism by which Cxcl12 exert its protective role in AML in vivo remain unresolved. We have evaluated the functional role of Cxcl12 secreted by early mesenchymal stromal cells (MSCs) and osteolineage committed cells in acute myeloid leukemia (AML) maintenance in vivo. Our results demonstrate that early MSCs, in contrast to committed osteoblasts, are integral part of the MLL::AF9 derived AML niche and control LSCs maintenance through Cxcl12 secretion. Cxcl12 from MSCs regulates the oxidative state of LSCs and promotes energy metabolism. Furthermore, the protective role of the niche through the activation of the CXCL12-CXCR4 axis, may also represent a biological hallmark in human pediatric and adult AML, hence, reinforcing the notion that targeting the MSCs-derived CXCL12 may help eradicate leukemia.

2022-11-01 | GSE189928 | GEO

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [tumor]

Project description:CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [tumor]

| PRJNA1153577 | ENA

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [scRNA-seq]

Project description:Niche-associated signals, essential for the maintenance of normal stem cells and tumor-initiating cells, are spatially confined and exert their influence locally among adjacent cells. Here, we demonstrate that CXCR4+ macrophages are enriched in the normal mammary ducts and enhance regenerative activity in basal cells in response to the CXCL12 secreted by luminal cells. Conditional knockout of CXCR4 in macrophages or CXCL12 in luminal cells results in similar phenotypes, including impaired branching morphogenesis, decreased regenerative functionality in basal cells, and diminished ductal association of macrophages. CXCL12 stimulation of macrophages triggers an AKT-mediated stabilization of β-catenin, increasing the expression of pro-migratory genes and multiple Wnt ligands, which enhances the infiltration of macrophages and their ability to support stem-like regenerative functions of basal cells. Importantly, the identical CXCR4+ niche macrophages also govern the tumor-initiating activity of breast tumors by promoting the survival and tumor-forming capacity of tumor-initiating cells and inducing early immune evasion through the accumulation of regulatory T cells. Our findings elucidate a crucial role of the CXCL12-CXCR4 axis in facilitating a complex interaction among niche macrophages, two mammary epithelial cell lineages, and other stromal components, thereby establishing a supportive environment for both normal tissue regeneration and mammary tumor initiation.

2025-04-15 | GSE275907 | GEO

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [tumor]

2025-04-15 | GSE275906 | GEO

CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia

Project description:Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia cells in vivo without impairing their homing to the bone marrow. In contrast, the CXCR4- ligand CXCL12 is dispensable for leukemia development in recipient mice. Moreover, expression of mutated Cxcr4 variants reveals that CXCR4 signaling is essential for leukemia cells. Notably, loss of CXCR4 signaling in leukemia cells leads to oxidative stress and differentiation in vivo. Taken together, our results identify CXCR4 signaling as essential for AML stem cells by protecting them from differentiation independent of CXCL12 stimulation.

2019-11-15 | GSE135275 | GEO

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary gland stem cells

Project description:CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary gland stem cells

| PRJNA1091707 | ENA

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [scRNA-seq]

Project description:CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [scRNA-seq]

| PRJNA1153578 | ENA

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary gland development and tumorigenesis

Project description:CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary gland development and tumorigenesis

| PRJNA1153573 | ENA

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary gland stem cells

Project description:Niche-associated signals, essential for stem cell maintenance, are spatially confined and exert their influence locally among adjacent cells. Here, we demonstrate that CXCR4+ macrophages are enriched in the mammary ducts and enhance MaSC activity in basal cells in response to the CXCL12 secreted by luminal cells. Conditional knockout of CXCR4 in macrophages or CXCL12 in luminal cells results in similar phenotypes, including impaired branching morphogenesis, decreased stem cell functionality in basal cells, and diminished ductal association of macrophages. CXCL12 stimulation of macrophages triggers an AKT-mediated stabilization of β-catenin, increasing the expression of pro-migratory genes and multiple Wnt ligands. This process enhances the infiltration of macrophages into intraepithelial regions and their ability to support MaSC functions. Our findings elucidate a crucial role of the CXCL12-CXCR4 axis in facilitating a complex interaction among ductal macrophages and two mammary epithelial cell lineages in establishing a supportive environment for MaSCs during mammary gland development.

2025-04-15 | GSE262432 | GEO

CXCL12/CXCR4 signaling mediates niche occupancy and tumor maintenance in T-cell leukemia

Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by infiltration of the bone marrow and other sites with transformed T cell progenitors. The role of tissue microenvironments in the pathogenesis of T-ALL or any other type of acute leukemia is little understood. In delineating interactions between T-ALL cells and their environment, we initially found that T-ALL cells express high surface levels of the chemokine receptor CXCR4. Intravital imaging of an intact tibia revealed T-ALL cells in direct contact with bone marrow stromal cells producing the CXCR4 ligand, CXCL12. Genetic targeting of CXCR4 on T-ALL cells resulted in a marked reduction of leukemia burden and prolonged disease remission, and disruption of the CXCL12/CXCR4 axis using small molecule inhibitors prevented T-ALL progression in a primary xenograft model. Finally, we were able to show that CXCR4 inhibition significantly decreased expression of Myc and its target genes. Myc expression is a key regulator of T-ALL leukemia initiating cell (LIC) activity, suggesting that CXCR4 inhibition can suppress LIC activity by silencing the Myc response in T-ALL cells. Our data suggest that targeting of CXCL12/CXCR4 signaling could be a powerful new tool for combating T-ALL, a disease with no current targeted therapies.

2015-08-12 | GSE60367 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data