Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics

ABSTRACT: Non-hematopoietic cells contribute essentially to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-Seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed Co-Detection by Indexing (CODEX) to spatially profile over one million single cells with a novel 53-antibody panel. We integrated scRNA-Seq and CODEX data to link cellular signaling and spatial proximity. Spatial analysis also revealed a hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, localization for early hematopoietic stem and progenitor cells. We used our CODEX atlas to automatically annotate cell types in new bone marrow images and uncovered MSC expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. This comprehensive, spatially-resolved multiomic atlas of human bone marrow serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253355 | GEO | 2024/04/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The role of HIF1 in enhancing radio resistance of mouse MSCs

Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSC have an efficient DNA damage response (DDR) and are consequently reatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif is involved in MSC radio-resistance, however its exact mechanism of action remains unknown. In order to dissect the involvement of Hif-1α in the DDR, we have generated using CRISPR/Cas9 technology, a stable MS5 mouse MSC cell line lacking Hif-1 expression. Herein, we show that it is the whole Hif-1 transcription factor, and not only the Hif-1α subunit, that modulates the DDR of mouse MSCs, and that this effect is dependent upon the integrity of the DNA binding domain. We have also characterized the Hif-1α-dependent proteomic changes undergone by hypoxic MS5 cells. These findings have important implications for the modulation of MSC radio-resistance in the context of BMT and cancer.

2018-05-16 | PXD006701 | Pride

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

Characterization of canine mesenchymal stromal cell lines (MSC)

Project description:The bone marrow microenvironment is a complex mixture of cells that function in concert to regulate hematopoiesis. Cellular components include fixed nonhematopoietic stromal elements (MSC) as well as monocytes and resident macrophages, which are derived from the hematopoietic stem cells. Clinical studies have shown healing effects, direct or indirect, from the injection of MSC int Keywords: Cell type comparison

2008-05-01 | GSE11310 | GEO

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

Inflammation of the Aged Bone Marrow Niche Drives Blood Aging

Project description:Hematopoietic aging is defined by a loss of regenerative capacity and skewed differentiation from hematopoietic stem cells (HSC) leading to dysfunctional blood production. Signals from the bone marrow (BM) microenvironment dynamically tailor hematopoiesis, but the effect of aging on the niche and the contribution of the aging niche to blood aging still remains unclear. Here, we show the development of an inflammatory milieu in the aged marrow cavity, which drives both niche and hematopoietic system remodeling. We find decreased numbers and functionality of osteogenic endosteal mesenchymal stromal cells (MSC), expansion of pro-inflammatory perisinusoidal MSCs, and deterioration of the central marrow sinusoidal endothelium, which together create a self-reinforcing inflamed BM milieu. Single cell molecular mapping of old niche cells further confirms disruption of cell identities and enrichment of inflammatory response genes. Inflammation, in turn, drives chronic activation of emergency myelopoiesis pathways in old HSCs and multipotent progenitors, which promotes myeloid differentiation at the expense of lymphoid and erythroid commitment, and hinders hematopoietic regeneration. Remarkably, both defective hematopoietic regeneration, niche deterioration and HSC aging can be improved by blocking inflammatory IL-1 signaling. Our results indicate that targeting the pro-inflammatory niche milieu can be instrumental in restoring blood production during aging.

2022-11-02 | GSE168613 | GEO

Signature of mesenchymal cell lines

Project description:We have analysed tes adipocytic, osteoblastic, chondrocytic and vascular smooth muscle differentiation of the stromal potential of 5 mouse mesenchymal lines derived from hematopoietic sites (bone marrow and fetal liver). The sole line, AFT024, that provide both quadripoential and capable of maintening hematopoiesis in vitro, has served as reference for genomic studies aimed at establishing the signature of the multipotential stromal mesenchymal stem cell (MSC). Keywords: molecular signature of MSC

2006-07-01 | GSE4491 | GEO

N-cadherin expressing bone and marrow stromal progenitor cells maintain reserve hematopoietic stem cells

Project description:Regulation of hematopoietic stem cells (HSCs) by bone marrow (BM) niches has been extensively studied; however, whether and how HSC subpopulations are distinctively regulated by BM niches remain unclear. Here, we functionally distinguished reserve HSCs (rHSCs) from primed HSCs (pHSCs) based on their response to chemotherapy and examined how they are dichotomously regulated by BM niches. Both pHSCs and rHSCs supported long-term hematopoiesis in homeostasis; however, pHSCs were sensitive but rHSCs were resistant to chemotherapy. Surviving rHSCs restored the HSC pool and supported hematopoietic regeneration after chemotherapy. The rHSCs were preferentially maintained in the endosteal region that enriches N-cadherin+ (Ncad+) bone-lining cells in homeostasis and post-chemotherapy. N-cad+ cells were functional bone and marrow stromal progenitor cells (BMSPCs), giving rise to osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Finally, ablation of Ncad+ niche cells or deletion of SCF from N-cad+ niche cells impaired rHSC maintenance during homeostasis and regeneration.

2019-01-15 | GSE104887 | GEO

Gene expression profile of murine bone marrow endosteal populations

Project description:This SuperSeries is composed of the following subset Series: GSE17569: Gene expression profile of murine bone marrow endosteal populations (1) GSE17570: Gene expression profile of murine bone marrow endosteal populations (2) Refer to individual Series

2010-08-10 | E-GEOD-17597 | biostudies-arrayexpress

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

Secretome Comparison of Mesenchymal Stromal Cells and Immature Osteoblasts

2021-11-15 | MSV000088384 | MassIVE