Breast cancer remotely imposes a myeloid bias on hematopoietic stem cells by reprogramming the bone marrow niche
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1020812 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26165256_1.fastq.gz | Fastqsanger.gz | |||
| SRR26165256_2.fastq.gz | Fastqsanger.gz | |||
| SRR26165257_1.fastq.gz | Fastqsanger.gz | |||
| SRR26165257_2.fastq.gz | Fastqsanger.gz | |||
| SRR26165258_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:Increased number of circulating myeloid cells is a hallmark of several cancers, however it remains unclear how primary tumors impact on myelopoiesis. Here we show that non-metastatic breast tumors remotely instruct the fate of long-term hematopoietic stem cell (HSCLT) in the bone marrow. We found that HSCLT from tumor bearing mice acquire a myeloid bias persisting upon primary and secondary HSCLT transfer in lethally-irradiated tumor-free animals. By imaging the bone marrow HSC niche, we found that the tumor-bearing status is associated with increased physical interactions between mesenchymal stem/stromal cells (MSC) and HSCLT. Moreover, ex vivo co-culture experiments demonstrate that MSC isolated from tumor-bearing mice increase myeloid differentiation of HSCLT isolated from tumor free mice. In summary, our data reveal that breast cancer remotely promotes myelopoiesis at the earliest stages of hematopoietic differentiation in the bone marrow mesenchymal niche.
2023-09-30 | GSE243964 | GEO
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
Project description:The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1-/-) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favors myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSCs quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche.
2018-06-21 | GSE114836 | GEO
Project description:Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation. Characterization of the transcriptome of fetal liver and adult bone marrow niche using RNA-seq
2015-12-03 | E-GEOD-72341 | biostudies-arrayexpress
Project description:Hematopoiesis advances cardiovascular disease by generating inflammatory leukocytes that attack the arteries, heart and brain. While it is well documented that the bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, it is less clear how cardiovascular disease affects the vasculature forming this niche. Here we show that arterial hypertension, atherosclerosis and myocardial infarction alter the anatomy and function of bone marrow vasculature. Hypertension and atherosclerosis instigated vascular fibrosis, leakage and endothelial dysfunction in the bone marrow. Myocardial infarction induced vascular leakage and bone marrow angiogenesis via Vegf signaling. Endothelial cell-specific deletion of the Vegf receptor 2 limited emergency hematopoiesis after myocardial infarction, indicating that new vasculature supports higher blood cell production. RNA-sequencing of bone marrow endothelial cells revealed inflammatory gene expression in mice with cardiovascular disease. Endothelial cell-specific deletion of interleukin 6 or versican, which were highly expressed in mice with atherosclerosis or myocardial infarction, respectively, reduced hematopoiesis and systemic myeloid cells. Taken together, cardiovascular disease affects the vascular bone marrow niche, thus influencing hematopoietic stem cell behavior and expanding innate immune cell supply to atherosclerotic plaque and ischemic myocardium. Interrupting this feed back loop may constrain cardiovascular inflammation.
2021-09-27 | GSE144498 | GEO
Project description:Local chronic inflammation exacerbates the prevalence and severity of associated distal organ comorbidities, causing catastrophic consequences for patients. However, the underlying mechanisms remain unclear. Here, we found that periodontitis increased the circulating pro-inflammatory neutrophils, which could be easily recruited to rheumatoid arthritis (RA) joints and aggravated articular destruction. Single-cell multiomics sequencing has revealed that periodontitis induces transcriptomic and epigenomic rewiring of hematopoietic stem and progenitor cells (HSPCs), which display skewed differentiation toward the neutrophil lineage, resulting in an increase in pro-inflammatory neutrophils. We further identified that periodontitis-elevated type I interferons are responsible for guiding the continuous neutropoiesis bias in the bone marrow. Resolution of periodontitis can reverse the differentiation bias of HSPCs and alleviate the progression of RA. This study indicated that neutropoiesis bias induces the progression of inflammatory comorbidities and emphasizes the necessity of controlling local chronic inflammation in the management of inflammatory comorbidities.
2025-05-12 | GSE236476 | GEO
Project description:Local chronic inflammation exacerbates the prevalence and severity of associated distal organ comorbidities, causing catastrophic consequences for patients. However, the underlying mechanisms remain unclear. Here, we found that periodontitis increased the circulating pro-inflammatory neutrophils, which could be easily recruited to rheumatoid arthritis (RA) joints and aggravated articular destruction. Single-cell multiomics sequencing has revealed that periodontitis induces transcriptomic and epigenomic rewiring of hematopoietic stem and progenitor cells (HSPCs), which display skewed differentiation toward the neutrophil lineage, resulting in an increase in pro-inflammatory neutrophils. We further identified that periodontitis-elevated type I interferons are responsible for guiding the continuous neutropoiesis bias in the bone marrow. Resolution of periodontitis can reverse the differentiation bias of HSPCs and alleviate the progression of RA. This study indicated that neutropoiesis bias induces the progression of inflammatory comorbidities and emphasizes the necessity of controlling local chronic inflammation in the management of inflammatory comorbidities.
2025-05-12 | GSE236479 | GEO
Project description:Bone marrow neutropoiesis bias underlies inflammatory comorbidities
| PRJNA991451 | ENA
Project description:Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM) that govern the delicate balance between HSC quiescence, self-renewal, and differentiation. It has been suggested that quiescent HSCs localize adjacent to BM arteriole endothelial cells in a significant and non-random distribution. This data suggests that the arteriole BM vascular niche may be the primary HSC niche. Because the BM arteriole niche is composed of tightly-associated pericytes, including smooth muscle actin+, LepR+, Nestin+, NG2+, and nonmyelinating Schwann cells, we sought to begin to uncouple the arteriole BM EC niche by examining its capacity to support the maintenance and expansion of HSCs ex vivo and in vivo. We developed a method to isolate and culture BM arteriole endothelial cells in serum-/growth factor-free conditions, allowing for a non-biased approach to examining their instructive function. Utilizing our protocol, we demonstrate that BM endothelial cells, but not BM stromal cells, have the capacity to expand long-term repopulating, multi-lineage HSCs in lieu of complex serum and cytokine supplementation. In addition, transplantation of arteriole endothelial cells promoted rapid hematopoietic recovery and protected HSCs following an LD50 dose of myeloablative irradiation. These data demonstrate that arteriole-derived BM endothelial cells are endowed with the necessary signals to support the self-renewal and regenerative capacity of LT-HSCs and that transplantation of arteriole BM endothelial cells could be used as a therapeutic means to decrease pancytopenias associated with myeloablative treatments to treat a wide array of disease states. Transcriptome sequencing of bone marrow endothelial cells and bone marrow stroma, in vitro and in vivo, with and without HSC co-culture.
2015-11-04 | E-GEOD-61636 | biostudies-arrayexpress