Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CXCR4 drives lympho-myeloid fate of hematopoietic progenitors via mTOR and mitochondrial metabolic pathways

ABSTRACT: Hematopoietic stem and progenitor cells (HSPCs), including the multipotent progenitors (MPPs), are responsible for replenishing immune cells. They reside in bone marrow (BM) endosteal and (peri)-vascular niches, which provide all cellular and molecular components required for their lifelong maintenance and fate. Among them, the CXCL12 chemokine and one of its receptor, CXCR4, exert a dominant role in promoting HSPC retention and quiescence. These processes are deregulated in the WHIM Syndrome (WS), a rare immunodeficiency caused by inherited heterozygous autosomal gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor. Clinically, WS is notably characterized by severe, chronic circulating lymphopenia whose mechanisms remain to be elucidated. Using a mouse model carrying a naturally occurring WS-linked Cxcr4 mutation, we explored the possibility that the lymphopenia in WS originates from defects at the MPP level in BM. The global strategy consists in performing high-throughput RNA-seq analyses of the different MPP subsets bearing or not the WS-linked Cxcr4 mutation to investigate the impact of the gain-of-Cxcr4-function on the molecular identity of MPP subsets.

ORGANISM(S): Mus musculus

PROVIDER: GSE182992 | GEO | 2021/09/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNAseq transcriptome analysis reveals developmental heterogeneity among mouse bone marrow monocyte subsets

Project description:Purpose: In our study, we identified a heterogeneity among bone marrow (BM) Ly6Chi monocytes, which can be subdivided the expression of CXCR4. In order to understand the development of BM monocytes, the goal of this experiment is to compare the transcriptome of these 2 BM Ly6Chi monocyte subsets to those of the common monocyte progenitor (cMoP) and Ly6Clo monocytes.

2016-09-29 | GSE86079 | GEO

Analysis of mouse central bone marrow versus endosteal transcriptome to define the hematopoietic stem cell niche at the endosteum

Project description:Stem cell function is regulated by specialized microenvironments called stem cell niches. These niches maintain stem cells in a dormant state and promote self-renewal. The most potent hematopoietic stem cells (HSC) with high self-renewal potential are reportedly enriched in the endosteal compared to the central region of the bone marrow. Therefore we analyzed the global transcriptome of the endosteal region and directly compared it to that of the central bone marrow (BM). This comparative, differential analysis revealed that in addition to genes specific to the osteoblastic and osteoclastic lineage and classic regulators of HSC (CXCL12, KIT ligand, angiopoietin-1, Jagged-1, N-cadherin), the endosteum abundantly expresses prostaglandin I2 (PGI2) synthase (Ptgis), which produces PGI2. PGI2 is a highly labile, lipid metabolite with no known roles in regulating HSCs. We show in this study that PGI2 is a potent regulator of HSC function. Therefore comparing endosteal versus central BM transcriptome is a viable approach for uncovering candidate genes that may regulate the function of HSC and the HSC niche.

2021-08-01 | GSE25078 | GEO

Mouse BM ILC progenitor subsets

Project description:Mouse BM ILC progenitor subsets

| PRJNA798063 | ENA

Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4

Project description:Obesity, a prevalent condition in adults and children, impairs bone marrow (BM) function. However, the underlying mechanisms are unclear. Here we show that obese mice exhibit poor emergency immune responses in a toll-like receptor 4 (TLR4)-dependent manner. Canonical myeloid genes (Csf1r, Spi1, Runx1) are enhanced, and lymphoid genes (Flt3, Tcf3, Ebf1) are reduced. Using adoptive transfer and mixed BM chimera approaches we demonstrate that myeloid>lymphoid bias arises after six weeks of high fat diet and depends on precursor cell-autonomous TLR4. Further, lean mice exposed to the TLR4 ligand lipopolysaccharide (LPS) at doses similar to that detectable in obese serum recapitulates BM lympho-myeloid alterations. Together, these results establish a mechanistic contribution of BM cell-intrinsic TLR4 to obesity-driven BM malfunction and demonstrate the importance of LPS. Our findings raises important questions about the impact of maternal obesity and endotoxemia to fetal hematopoiesis, as fetal immune precursors are also sensitive to TLR4 signals.

2018-01-17 | GSE109269 | GEO

Functional and transcriptional heterogeneity of human hemopoietic lympho-myeloid progenitors

Project description:Cord blood (CB) samples from normal donors were obtained with informed consent. Fresh CB samples were processed within 18-34h after collection. Mononuclear cells were isolated and CD34+ fraction was separated. CB CD34+ enriched fraction was lineage depleted by staining with purified anti-human CD2, CD3, CD4, CD7, CD8a, CD11b, CD14, CD19, CD20, CD56, CD235a followed by Qdot 605 conjugated goat F(ab')2 anti-mouse IgG (H+L). Cells were also stained with anti-human CD38-FITC, CD45RA-PE or -BV650, CD123-PE Cy7, CD90-biotin, CD34- PerCP and CD10-APC. Finally, cells were incubated with streptavidin-conjugated APC-eF780 and Hoechst 33258 (Invitrogen, final concentration: 1 g/ml). Populations were defined, as follows: HSC - Lin-CD34+CD38-CD90+CD45RA-CD10-, MPP - Lin-CD34+CD38-CD90-CD45RA-CD10-, LMPP - Lin-CD34+CD38-CD90-/loCD45RA+CD10-, MLP - Lin-CD34+CD38-CD90-/loCD45RA+CD10+, GMP - Lin-CD34+CD38+CD123+CD45RA+CD10-, CMP - Lin-CD34+CD38+CD123+CD45RA-CD10-, MEP - Lin-CD34+CD38+CD123-CD45RA-CD10-.

2017-10-03 | E-MTAB-5456 | biostudies-arrayexpress

Differential Peak Calling of ChIP-Seq Signals with Replicates with THOR

Project description:Dendritic cells (DC) are professional antigen presenting cells that develop from hematopoietic stem cells in bone marrow by successive steps of lineage commitment and differentiation. Different DC subsets were identified based on phenotype, localisation and function: (i) classical DC (cDC) and plasmacytoid DC (pDC) are found in lymphoid organs and (ii) migratory tissue DC are spread throughout peripheral organs, including Langerhans cells, the cutaneous contingent of DC. We have developed a two-step culture system that recapitulates DC development in vitro (Felker et al., J. Immunol. 185, 5326-5335, 2010). In this system multipotent hematopoietic progenitors (MPP) progress into DC-restricted common DC progenitors (CDP) and further into the two major DC subsets cDC and pDC. We employed chromatin immunoprecipitation (ChIP) with deep sequencing (ChIP-seq) to determine the dynamics of H3K27ac occupancy in MPP, CMP, cDC and pDC. Histone modification H3K27ac and RNA-Seq in MPP, CDP, cDC and pDC

2016-08-03 | E-GEOD-73143 | biostudies-arrayexpress

Transcriptomic characterisation of phenotypic haematopoietic stem cells from human adult bone marrow, spleen and peripheral blood

Project description:Haematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), the precursors of all blood cells, reside predominantly in the bone marrow (BM). Recent evidence suggests that other anatomical sites may contribute significantly to blood production, but the cellular, molecular and functional composition of extramedullary HSC/MPP pools remains unexplored. Here, we have compared the transcriptomes of single cells sorted from the phenotypic HSC/MPP pool of adult bone marrows and spleens from the same donors.

2020-01-14 | GSE143567 | GEO

Location of indigenous human HSCs reveals functional properties of HSCs that are dictated by anatomic and cellular architecture of bone marrow I

Project description:Demonstration of hematopoietic stem cells (HSCs) was first shown in the mouse and was dependent on recipient bone marrow (BM) to support in vivo multilineage hematopoietic reconstitution, thereby illustrating non-cell-autonomous requirements for HSC functions. Murine studies have defined microanatomic compartments in the BM comprised of osteoblasts, mesenchymal cells, subsets of vasculature, and innervating neural cells functioning as an HSC-supportive niche. Despite the potential clinical applications, analyses of putative HSCs in the BM of humans has not been examined. Here, using human bone biopsies, we provide evidence of HSC propensity to endosteal regions of Trabecular Bone Area (TBA). Independent of phenotypic definitions based on prospective isolation, functional studies indicate that human HSCs residing in the TBA of human and transplanted recipients had superior regenerative and self-renewal capacity and are molecularly distinct to those repopulating the Long Bone Area (LBA). Consistent with the non-cell-autonomous nature of HSC function, osteoblasts in the TBA possess unique characteristics and expressed a key network of factors including those involving Notch activity which could regulate TBA vs. LBA location of human HSCs in vivo. Our study illustrates that human-mouse xenografts provide a surrogate to indigenous human HSC in the BM, and demonstrates that BM architecture plays a critical role in defining functional properties of human HSCs.

2013-08-01 | GSE47934 | GEO

Location of indigenous human HSCs reveals functional properties of HSCs that are dictated by anatomic and cellular architecture of bone marrow II

2013-08-01 | GSE47935 | GEO

Effect of the gain-of-function mutation of CXCR4 on the molecular identity of murine Skeletal Stromal/Stem Cells (SSC) and OsteoProgenitor Cells (OPC)

Project description:In order to perform transcriptional analyses of two stromal subsets carrying the gain-of-function mutation of CXCR4, bulk RNA Sequencing (RNA-Seq) was conducted on SSC and OPC sorted from WT (Cxcr4+/+) , heterozygous (Cxcr4+/1013) and homozygous (Cxcr41013/1013) mutant mice for Cxcr4.

2023-02-06 | GSE217422 | 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