CD54+CD31-BP1+ and CD54-CD31+ bone marrow cells from wild type mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE90586 | GEO | 2019/03/01
REPOSITORIES: GEO
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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
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
Project description:Fate decisions of haematopoietic stem cells (HSCs) to self-renew or differentiate in response to various demands are finely tuned by specialized microenvironments called “niches” in the bone marrow. Recent studies suggest that arterioles and sinusoids accompanied with distinct stromal cells marked by nerve/glial antigen 2 (NG2) and leptin receptor (LepR), compose distinct niches regulating quiescence and proliferation of HSCs, respectively. However, it remains unknown how the distinct niche cells differentially regulate the HSC functions. Here we show that effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (CXCL12) in NG2-cre targeted cells, which exclusively overlap with Nestin-GFP (Nes-GFP)+ stromal cells associated with arterioles and sinusoids, resulted in a robust reductions of HSCs in the bone marrow and massive mobilization. Deletion of CXCL12 from arteriolar NG2+ vascular smooth muscle cells caused a significant decrease of HSCs and altered HSC location in the marrow, while CXCL12 depletion from sinusoidal LepR+ cells did not reduce HSC numbers in the bone marrow. By contrast, deletion of stem cell factor (SCF) in LepR+ cells led to significant reductions in HSC numbers whereas SCF deletion in arteriolar NG2+ cells showed no effect on HSC numbers in the marrow. These results uncover the distinct contributions of cytokines derived from perivascular cells in separate vascular niches for HSC maintenance and mobilization. We sought to obtain comprehensive understanding of differences between peri-arteriolar and peri-sinusoidal niche cells by the present RNA-seq analysis.
2017-02-19 | GSE89811 | GEO
Project description:Adult hematopoietic stem cells (HSCs) reside primarily in bone marrow. However, hematopoietic stresses such as myelofibrosis, anemia, pregnancy, infection or myeloablation can mobilize HSCs to the spleen and induce extramedullary hematopoiesis (EMH). While the bone marrow HSC niche has been studied intensively, the EMH niche has received little attention. Here, we systematically assessed the physiological sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by cyclophosphamide plus granulocyte colony-stimulating factor, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow hematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create the splenic EMH niche, which is necessary for the physiological response to diverse hematopoietic stresses. Unfractionated spleen cells (2 replicates) and FACS-sorted VE-cadherein negative Scf-GFP positive cells (3 replicates)
2015-08-01 | E-GEOD-71288 | biostudies-arrayexpress
Project description:Adult hematopoietic stem cells (HSCs) reside primarily in bone marrow. However, hematopoietic stresses such as myelofibrosis, anemia, pregnancy, infection or myeloablation can mobilize HSCs to the spleen and induce extramedullary hematopoiesis (EMH). While the bone marrow HSC niche has been studied intensively, the EMH niche has received little attention. Here, we systematically assessed the physiological sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by cyclophosphamide plus granulocyte colony-stimulating factor, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow hematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create the splenic EMH niche, which is necessary for the physiological response to diverse hematopoietic stresses.
2015-08-01 | GSE71288 | GEO
Project description:RNA-sequencing of a longitudinal comparison of four principal mesenchymal and endothelial stromal cell types (CXCL12-abundant reticular cells, PDGFR-α+ Sca-1+, sinusoidal and arterial endothelial cells), isolated from early postnatal, adult and aged mice. Additional transcriptional profiling of the response of CXCL12-abundant reticular cells and sinusoidal endothelial cells to infection-mimicking agents.
2019-12-16 | GSE133922 | GEO
Project description:With ageing, intrinsic hematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing affects also the HSC niche impairing the capacity to support HSC function is still largely unknown. Here, by using in-vivo long-term label retention assays we demonstrate that aged labelling retaining (LR) HSCs, which are in the old mice the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches and perisinusoidal Nes-GFPlow cells are uniquely preserved in shape, morphology and number upon ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches, which is linked to hematopoietic failure and decreased survival of aged mice. Overall, our data characterize for the first time the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and protect HSCs from ageing.
2019-09-02 | GSE129726 | GEO
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.
2013-01-31 | E-GEOD-43613 | biostudies-arrayexpress
Project description:In this study, we show that targeted deletion of CXCL12 from mesenchymal stromal cells (MSC) reduces normal HSC numbers, but in contrast expands murine LSC numbers by increasing self-renewing cell divisions, related to enhanced EZH2 activity. CML development leads to emergence of abnormal niches of MSC and LSC clusters that are lost upon CXCL12 deletion. Importantly, CXCL12 deletion from MSC also increases LSC elimination by TKI treatment. These studies reveal a critical role for CXCL12-expressing MSC niches in maintaining a population of quiescent, TKI-resistant LSC, and support targeting of these niche interactions to enhance LSC elimination.
2019-04-02 | GSE124125 | GEO
Project description:Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSC in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging technique and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare Nestin-GFP-peri/NG2+ pericytes, distinct from sinusoid-associated Nestin-GFP-retic/LepR+ cells. The present RNA-seq study sought to obtain a comprehensive understanding of the differences between the two distinct HSC cellular niches. mRNA profiles of sorted Nestin-GFP-peri and -GFP-retic bone marrow stromal cells were generated from pooled mice in triplicate by Illumina HiSeq 2000 sequencing.
2013-10-10 | E-GEOD-48764 | biostudies-arrayexpress