Dataset's files
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| GSE270983_RAW.tar | Raw | |||
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Similar Datasets
Project description:Bone metastasis significantly compromises quality of life in advanced-stage breast cancer patients through severe pain, fractures, and decreased mobility. The role of bone-resident cells such as osteoblasts and osteoclasts in metastatic interactions is well-established, however, the contribution of hematopoietic stem cell (HSC) lineage cells in the bone marrow, which differentiate into both red and white blood cells, remains poorly understood. Employing an in vivo metastatic niche labeling system and single-cell RNA sequencing, we systematically identified and functionally validated novel stromal components critical for bone metastasis. This niche labeling system enabled metastatic cancer cells to directly label surrounding niche cells in vivo via mCherry secretion. Bone marrow cells proximal to the tumor, which absorbed the secreted mCherry, were characterized using single-cell RNA sequencing. Our analysis revealed a distinct macrophage population enriched in the metastatic niche. Further in-depth characterization of these niche-specific macrophages was performed through cell sorting and bulk RNA sequencing. This population was found to be specialized macrophages with iron metabolism capabilities, residing within the erythroid island to support erythropoiesis. We demonstrated that in the bone metastasis environment breast cancer cells hijacked the iron-rich macrophages to supply themselves with iron. To better survive in the hypoxic bone marrow microenvironment, tumor cells mimic erythroblasts by upregulating globin gene expression and heme synthesis genes. These findings underscore the critical role of iron-rich macrophages in supporting tumor growth in the bone and their significant impact on erythropoiesis, presenting novel therapeutic targets for managing bone metastasis and cancer-related anemia.
2025-08-20 | GSE270982 | GEO
Project description:Bone metastasis significantly compromises quality of life in advanced-stage breast cancer patients through severe pain, fractures, and decreased mobility. The role of bone-resident cells such as osteoblasts and osteoclasts in metastatic interactions is well-established, however, the contribution of hematopoietic stem cell (HSC) lineage cells in the bone marrow, which differentiate into both red and white blood cells, remains poorly understood. Employing an in vivo metastatic niche labeling system and single-cell RNA sequencing, we systematically identified and functionally validated novel stromal components critical for bone metastasis. This niche labeling system enabled metastatic cancer cells to directly label surrounding niche cells in vivo via mCherry secretion. Bone marrow cells proximal to the tumor, which absorbed the secreted mCherry, were characterized using single-cell RNA sequencing. Our analysis revealed a distinct macrophage population enriched in the metastatic niche. Further in-depth characterization of these niche-specific macrophages was performed through cell sorting and bulk RNA sequencing. This population was found to be specialized macrophages with iron metabolism capabilities, residing within the erythroid island to support erythropoiesis. We demonstrated that in the bone metastasis environment breast cancer cells hijacked the iron-rich macrophages to supply themselves with iron. To better survive in the hypoxic bone marrow microenvironment, tumor cells mimic erythroblasts by upregulating globin gene expression and heme synthesis genes. These findings underscore the critical role of iron-rich macrophages in supporting tumor growth in the bone and their significant impact on erythropoiesis, presenting novel therapeutic targets for managing bone metastasis and cancer-related anemia.
2025-08-20 | GSE270981 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-04-10 | GSE108892 | GEO
Project description:BackgroundTrauma is associated with widespread inflammation, neuroendocrine activation, and an inadequate bone marrow response to anemia. During late-stage erythropoiesis, erythroid progenitors/erythroblasts form clusters on the surface of specialized bone marrow macrophages where they are supported through terminal differentiation and enucleation. We hypothesized that these erythroblastic islands (EBIs) are adversely impacted by severe trauma.MethodsMale Sprague-Dawley rats (n = 8/group) were subjected to either multiple injuries (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus 2 hours of daily chronic restraint stress (PT/CS), or naive controls. Bone marrow was harvested on days 2 and 7. Nuclear-stained, enriched bone marrow EBIs were fixed and stained for CD71, VCAM-1, and CD163, and confocal images were obtained at 20 times magnification. Numbers of erythroid cells/EBI and ratio of reticulocytes/EBI were counted by a blinded observer. Differences were compared using analysis of variance, with significance defined as p < 0.05.ResultsPT and PT/CS had significantly reduced numbers of erythroid cells per EBI on day 2 when compared with naive (PT: 5.9 ± 1.0 cells [ p < 0.05], PT/CS: 6.8 ± 0.8 cells [ p < 0.05] vs. naive: 8.5 ± 0.8 cells). On day 7, the number of erythroid cells/EBI increased following PT (8.3 ± 0.4 cells) but remained reduced following PT/CS (5.9 ± 0.5 cells [ p < 0.05]). This correlated with an increased proportion of reticulocytes/EBI on day 7 following PT, which was not present following PT/CS (PT: 54% [ p < 0.05] vs. PT/CS: 28%).ConclusionLate-stage erythropoiesis was altered following multicompartmental PT early after injury, and these alterations persisted with the addition of daily chronic stress. Alterations in EBI structure and function after severe trauma and critical illness may serve as a promising new area of study to improve mechanistic understanding of persistent anemia after trauma.
| S-EPMC9877140 | biostudies-literature
Project description:Adipocyte infiltration in the bone marrow follows chemotherapy or irradiation. Previous studies indicate that bone marrow fat cells inhibit hematopoietic stem cell function. Recently, Zhou et al. (2017) using state-of-the-art techniques, including sophisticated Cre/loxP technologies, confocal microscopy, in vivo lineage-tracing, flow cytometry, and bone marrow transplantation, reveal that adipocytes promote hematopoietic recovery after irradiation. This study challenges the current view of adipocytes as negative regulators of the hematopoietic stem cells niche, and reopens the discussion about adipocytes' roles in the bone marrow. Strikingly, genetic deletion of stem cell factor specifically from adipocytes leads to deficiency in hematopoietic stem cells, and reduces animal survival after myeloablation, The emerging knowledge from this research will be important for the treatment of multiple hematologic disorders. © 2017 International Society for Advancement of Cytometry.
| S-EPMC6067923 | biostudies-literature
Project description:The cardinal property of bone marrow (BM) stromal cells is their capacity to contribute to hematopoietic stem cell (HSC) niches by providing mediators assisting HSC functions. In this study we first contrasted transcriptomes of stromal cells at different developmental stages and then included large number of HSC-supportive and non-supportive samples. Application of a combination of algorithms, comprising one identifying reliable paths and potential causative relationships in complex systems, revealed gene networks characteristic of the BM stromal HSC-supportive capacity and of defined niche populations of perivascular cells, osteoblasts, and mesenchymal stromal cells. Inclusion of single-cell transcriptomes enabled establishing for the perivascular cell subset a partially oriented graph of direct gene-to-gene interactions. As proof of concept we showed that R-spondin-2, expressed by the perivascular subset, synergized with Kit ligand to amplify ex vivo hematopoietic precursors. This study by identifying classifiers and hubs constitutes a resource to unravel candidate BM stromal mediators.
| S-EPMC7300160 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-23 | GSE183152 | GEO
Project description:BackgroundThe bone/bone marrow is one of the most common sites for metastatic solid tumors. Moreover, the tumor microenvironment is an essential part of cancer homeostasis. Previously, it was shown that cytochrome P450 enzymes (CYPs) are present in the bone marrow (BM) microenvironment, particularly in the mesenchymal stroma cells, at levels comparable to those of hepatocytes. It was found that the CYPs play important roles in nurturing and maintaining normal hematopoietic stem cells as well as multiple myeloma and leukemia cells, including protecting them from toxic insults. It was hypothesized that the CYPs in the BM microenvironment might play a similar role in solid tumors metastatic to bone.MethodsThe interaction between the BM microenvironment and malignant cells that routinely metastasize to the bone (lung, breast, and prostate cancer) was modeled. Via genetic engineering and pharmacological approaches, the role of stromal cytochrome P450 3A4 (CYP3A4) in drug resistance promoted by the BM microenvironment in niche-cancer models in vitro and in vivo was interrogated.ResultsBM stroma protected prostate, breast, and lung cancer cells from cytotoxic chemotherapy. Stromal CYP3A4 was at least partially responsible for this protection in vitro and in vivo. Moreover, inhibiting CYP3A4 with clarithromycin overcame the stroma-mediated chemoresistance toward prostate, breast, and lung cancer cells.ConclusionsThese results suggest that, similar to observations from hematologic malignancies, the BM microenvironment, through expression of CYPs, creates a sanctuary site from chemotherapy for metastatic solid tumors. Targeting these sanctuaries holds promise for eradicating bone metastasis in solid tumors.
| S-EPMC10966383 | biostudies-literature
Project description:The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice. We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tumour-specific growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permissive niche for incoming tumour cells. Conditioned media obtained from distinct tumour types with unique patterns of metastatic spread redirected fibronectin expression and cluster formation, thereby transforming the metastatic profile. These findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread.
| S-EPMC2945882 | biostudies-literature
Project description:Bone marrow is a heterogeneous organ containing diverse cell types, and it is a preferred metastatic site for several solid tumors such as breast and prostate cancer. Recently, it has been shown that bone metastatic cancer cells interact with the bone marrow microenvironment to survive and grow, and thus this microenvironment is referred to as the 'metastatic niche'. Once cancer cells spread to distant organs such as bone, the prognosis for the patient is generally poor. There is an urgent need to establish a greater understanding of the mechanisms whereby the bone marrow niche influences bone metastasis. Here we discuss insights into the contribution of the bone marrow 'metastatic niche' to progression of bone metastatic disease, with a particular focus on cells of hematopoietic and mesenchymal origin.
| S-EPMC4440229 | biostudies-other