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Stromal inflammation is a targetable driver of blood aging [droplet-based scRNAseq - Batch 2]

ABSTRACT: To investigate the role of IL1 signaling in hematopoietic aging, we performed droplet-based scRNAseq (10X Genomics) of hematopoietic stem and progenitor cells (LK/LSK) and unfractionated endosteal and central marrow stromal cells (Ter119-/CD45-) from young wild type and young and old wild type and IL1R1-/- C57BL/6 mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE189217 | GEO | 2022/11/02

REPOSITORIES: GEO

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Stromal inflammation is a targetable driver of hematopoietic aging [droplet-based scRNAseq]

Project description:To investigate global changes in the structure of the bone marrow niche with age, we performed droplet-based scRNAseq (10X Genomics) of unfractionated endosteal and central marrow stromal cells (Ter119-/CD45-). 8,735 cells passed QC, and hematopoietic clusters of cells were excluded based on marker gene expression, leaving 2359 cells distributed across 9 distinct clusters for final presentation.

2022-11-02 | GSE168586 | GEO

Gene expression profile of murine bone marrow endosteal populations (1)

Project description:A subset of osteoblasts functions as a key component of the hematopoietic stem cell niche. But it is still unclear that the precise cellular and molecular contribution of endosteal cell populations on the HSC supportive microenvironment. We purified the endosteal cells and subdivided them into mesenchymal progenitor cells (MPCs: ALCAM(-)Sca-1(+)) and two osteoblast populations (ALCAM(-)Sca-1(-) and ALCAM(+)Sca-1(-)). In this study, to clarify the characteristics of these fractionated cells in detail, gene expression analysis were performed using the GeneChip Mouse Genome Array 430 2.0 (Affymetrix). The bone fragments of femur and tibiae were treated with collagenase and endosteal cells were obtained. For enrichment of non-hematopoietic and non-endothelial population, CD45(-)CD31(-)Ter119(-) population was isolated and then the expressions of Sca-1 and activated leukocyte cell adhesion molecule (ALCAM) was analyzed by FACS. FACS analysis showed that CD45(-)CD31(-)Ter119(-) cells were subdivided into ALCAM(-)Sca-1(+), ALCAM(-)Sca-1(-) and ALCAM(+)Sca-1(-). These three populations were sorted and RNA samples were used for amplification, labeling, and hybridization to independent arrays.

2010-08-10 | E-GEOD-17569 | biostudies-arrayexpress

Gene expression profile of murine bone marrow endosteal populations (2)

Project description:A subset of osteoblasts functions as a key component of the hematopoietic stem cell niche. But it is still unclear that the precise cellular and molecular contribution of endosteal cell populations on the HSC supportive microenvironment. We purified the endosteal cells and subdivided them into mesenchymal progenitor cells (MPCs: PDGF-Ra(+)Sca-1(+)) and two osteoblast populations (PDGF-Ra(-)Sca-1(-) and PDGF-Ra(+)Sca-1(-)). In this study, to clarify the characteristics of these fractionated cells in detail, gene expression analysis were performed using the GeneChip Mouse Genome Array 430 2.0 (Affymetrix). The bone fragments of femur and tibiae were treated with collagenase and endosteal cells were obtained. For enrichment of non-hematopoietic and non-endothelial population, CD45(-)CD31(-)Ter119(-) population was isolated and then the expressions of Sca-1 and PDGF-Ra was analyzed by FACS. FACS analysis showed that CD45(-)CD31(-)Ter119(-) cells were subdivided into PDGF-Ra(+)Sca-1(+), PDGF-Ra(-)Sca-1(-) and PDGF-Ra(+)Sca-1(-). These three populations were sorted and RNA samples were used for amplification, labeling, and hybridization to independent arrays.

2010-08-10 | E-GEOD-17570 | biostudies-arrayexpress

Secretome Comparison of Mesenchymal Stromal Cells and Immature Osteoblasts

Project description:Osteoblasts are a key component of the endosteal hematopoietic stem cell (HSC) niche and have long been recognized with strong hematopoietic supporting activity. Osteoblast conditioned media (OCM) enhances the growth of hematopoietic progenitors in culture and modulate their engraftment activity. We aimed to characterize the hematopoietic supporting activity of OCM by comparing the secretome of immature osteoblasts to that of their precursor, mesenchymal stromal cells (MSC). Over 300 secreted proteins were quantified by mass spectroscopy in media conditioned with MSC or osteoblasts, with 47 being differentially expressed.

2020-07-17 | PXD017372 | Pride

Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation

Project description:RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Scf; GFP+Cxcl12; DsRed+ bone marrow stromal cells ,2D cultured bone marrow stromal cells and 3D cultured bone marrow stromal cells. RNA sequencing data of sorted primary and 3D cocultured Lin-Sca1+C-kit+CD150+CD48+ hematopoietic stem cells from 8-12 weeks and 12-13 months old mice. RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Pdgfra+td-Tomato+ bone marrow stromal cells from young (8 wks), middle aged (12 months) and aged (22-24 months) Lepr-Cre;td-Tomato mice.

2023-04-06 | GSE180866 | GEO

DNA hypomethylation leads to derepression of myeloerythroid genes in hematopoietic stem cells (HSC)

Project description:Analysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice

2009-10-06 | GSE17765 | GEO

Selective endosteal remodeling of blood vessels in acute myeloid leukemia promotes malignancy at the expense of hematopoietic stem cells

Project description:Hematopoietic stem cell (HSC) function requires bone marrow vascular niches, which have been proposed to be co-opted by leukemia cells to support their propagation. Acute myeloid leukemia (AML) cells produce angiogenic factors; however, anti-angiogenic therapies have not improved AML patient outcome. Using intravital microscopy we uncovered hierarchical vascular remodeling with AML progression. AML cells outcompete non-malignant hematopoiesis by gradual elimination of stroma cells, endosteal endothelium, and osteoblastic cells. While central marrow remains vascularized and splenic vascular niches expand, the remodeled endosteal regions lose the ability to retain HSCs. Overall, the endosteal endothelium microenvironment is altered by AML, yet by preserving it we rescue HSC loss and promote chemotherapeutic efficacy. Our findings suggest therapies targeting the endosteal vasculature may improve existing AML therapeutic regimes.

2017-11-01 | GSE105159 | GEO

Secretome Comparison of Mesenchymal Stromal Cells and Immature Osteoblasts

2021-11-15 | MSV000088384 | MassIVE

Transcription profiling of mouse hematopoietic stems cells and myeloid progenitor cells from wild type and Dnmt1 hypomorph mice shows DNA hypomethylation leads to derepression of myeloerythroid genes

Project description:Analysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice Experiment Overall Design: We FACS sorted HSCs and MPs from bone marrow of 8-12 week old wildtype or Dnmt1 hypomorph (Dnmt1-/chip) mice.

2009-10-09 | E-GEOD-17765 | biostudies-arrayexpress

Gene expression profile of murine bone marrow endosteal populations (2)

2010-08-10 | GSE17570 | GEO

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