Pericyte induced reprogramming of the bone marrow microenvironment drives stem and cancer cell quiescence
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB27368 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This dataset was generated by RNA sequencing of whole tibiae of C57Bl/6 mice. For young mice; tibiae from 6-weeks-old mice were used and for aged mice tibiae from 70-weeks-old mice were used. The control, radiation, and chemotherapy samples were generated using 14-weeks-old mice. For radiation treatment; mice were exposed to sublethal irradiation while for chemotherapy samples mice were treated with carboplatin and tibiae were collected
2019-06-05 | E-MTAB-6872 | biostudies-arrayexpress
Project description:Rpd3 drives transcriptional quiescence
| PRJNA279126 | ENA
Project description:Pericytes and endothelial cells (ECs) are building blocks of blood vessels. While the contributions of ECs to tumor angiogenesis and the tumor microenvironment are well established and multiple drugs that targeting ECs have been developed for clinic use to treat cancers, the underlying mechanisms of pericyte in supporting tumor vessel and in shaping tumor microenvironment remains largely unexplored and no pericyte targeting strategies have been approved yet. This study employs targeted deletion of the NO receptor sGC in pericytes and utilizes single-cell RNA sequencing to elucidate its impact on the tumor microenvironment. The results unveil a disruptive effect on EC-pericyte interactions, subsequently impeding Notch-mediated intercellular crosstalk and prompting extensive transcriptomic reprogramming in both cell types. This vascular alteration further relays to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Importantly, the inhibition of pericyte sGC has limited influence on quiescent vessels but significantly sensitizes angiogenic vessels to anti-angiogenic treatment. In conclusion, this study underscores the vital role of pericytes in governing tumor vessels and the tumor microenvironment, suggesting that targeting pericyte sGC holds promise for enhancing anti-angiogenic therapy.
2024-02-01 | GSE243313 | GEO
Project description:Pericyte induced reprogramming of the bone marrow microenvironment drives stem and cancer cell quiescence
2018-09-17 | E-MTAB-6872 | ExpressionAtlas
Project description: Not available
| S-EPMC8473680 | biostudies-literature
Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.
2018-10-24 | PXD006581 | Pride
Project description:One of the hallmarks of multiple myeloma (MM) is a permissive BM microenvironment. Increasing evidence suggest that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line - MOPC315.BM -, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as Granzyme b and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.
2022-07-05 | PXD032934 | Pride
Project description:Proteomics analysis can reveal the differences of protein expression between mural cells (known as pericytes) from normal adjacent tissues (NPC) and tumors (TPC), implying the effectiveness of pericyte to tumor.
2021-08-24 | PXD026963 | Pride
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 Aging Microenvironment Drives Alveolar Macrophage Changes in Aging
| PRJNA555068 | ENA