The Role of Bone Marrow Erythroblastic Niche in Supporting metastatic Growth [scRNA-Seq]
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PROVIDER: PRJNA1129150 | ENA |
REPOSITORIES: ENA
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Project description:The Role of Bone Marrow Erythroblastic Niche in Supporting metastatic Growth [BulkRNAseq]
| PRJNA1129149 | ENA
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:The erythroblastic island (EBI), composed of a central macrophage and surrounding erythroid cells, was the first hematopoietic niche discovered. The identity of EBI macrophages has thus far remained elusive. Gene expression profiles of BM F4/80+Epor-eGFP+ macrophages suggest a specialized function in supporting erythropoiesis.
2019-05-31 | GSE127980 | GEO
Project description:Identifying a perivascular niche supporting lung alveoli epithelial stem cells and metastatic cancer cells
| PRJNA759276 | ENA
Project description:Incomplete understanding of metastatic disease mechanisms continues to hinder effective treatment of cancer. Despite remarkable advancements toward the identification of druggable targets, treatment options for patients in remission following primary tumor resection remain limited. Bioengineered human tissue models of metastatic sites capable of recreating the physiologically relevant milieu of metastatic colonization may strengthen our grasp of cancer progression and contribute to the development of effective therapeutic strategies. We report the use of an engineered tissue model of human bone marrow (eBM) to identify microenvironmental cues regulating cancer cell proliferation and to investigate how triple-negative breast cancer cell lines influence hematopoiesis. Notably, individual stromal components of the BM niche (osteoblasts, endothelial cells, and mesenchymal stem/stromal cells) were each critical for regulating tumor cell quiescence and proliferation in the three-dimensional eBM niche. In this data set, we provide transcriptomic information from bulk RNA sequencing of MDA-MB-231 cancer cells that were pre-conditioned by being co-cultured on variations of eBM tissues. We envision that this human tissue model will facilitate studies of niche-specific metastatic progression and individualized responses to treatment.
2024-09-23 | GSE277786 | GEO
Project description:The erythroblastic island (EBI), composed of a central macrophage and surrounding maturing erythroblasts, is the erythroid precursor niche. Despite numerous studies, its precise composition is still unclear. Using multispectral imaging flow cytometry (IFC), in vitro island reconstitution, and single cell RNA-seq of EBI-component cells enriched by gradient sedimentation, we present evidence that CD11b+ cells present in the EBIs are neutrophil precursors specifically associated with bone marrow EBI macrophages, indicating that erythro-(myelo)-blastic islands are a site for terminal granulopoiesis as well as erythropoiesis and production of these lineages is dynamically regulated within this niche. We further demonstrate that the balance between these lineages is determined by pathophysiological conditions, favoring granulopoiesis during anemia of inflammation, or erythropoiesis after erythropoietin (Epo) stimulation. Finally, we provide the heterogeneous molecular profiling of EBI macrophages as revealed by Cellular Indexing of Transcriptome and Epitopes (CITE)-sequencing of mouse bone marrow EBIs at baseline and after Epo-stimulation in vivo. Altogether, these data demonstrate that EBIs serve a dual role as terminal erythropoiesis and granulopoiesis niches and the central macrophages adapt to the needs of stress erythropoiesis as well as granulopoiesis.
2022-07-22 | GSE196347 | GEO
Project description:The erythroblastic island (EBI) functions as a niche where erythroblastic island macrophages (EBIMφ) are positioned within rings of erythroblasts, providing support and signals that orchestrate efficient erythropoiesis. Herein, we postulated burn injury impacts the EBI, given the nearly universal presence of anemia and inflammation in burn patients, and a divergent myeloid transcriptional signature we observed in murine bone marrow following burn injury, where G-CSF secretion increased neutrophil and monocyte transcripts but reduced EBIMφ transcripts. We utilized flow cytometry to investigate EBIMφ after imaging flow cytometry confirmed the heme induced transcription factor Spi-C as a robust marker of EBIMφ in Spicigfp/igfp mice. Two populations referred to as Spic+ macrophages and Spic+ Gr1 low monocytes possessed cell intrinsic GFP, with Spic+ macrophages distinguished by higher levels of GFP, F4/80, autofluorescence, and negligible CD115 staining compared to Gr1 low monocytes. Further, at least 50% of the Spic+ macrophages stained for CD163 while staining was negligible on Gr1 low monocytes. Since CD163 distinguished the populations and macrophage remnants could convolute flow cytometry analysis, total CD163 protein was quantified in marrow aspirates to corroborate results. Application of Spicigfp/igfp mice in studies revealed a G-CSF dependent reduction of Spic+ macrophages in post burn marrow that coincided with a loss of erythroid cells and that recombinant G-CSF alone was sufficient to reduce Spic+ macrophages in the marrow. These results provide the first evidence that burn injuries impact the EBI niche through G-CSF dependent depletion of EBIMφ and support the use of Spicigfp/igfp mice in investigation of EBIMφ.
2024-12-09 | GSE263318 | GEO
Project description:Metastatic lesions are typically not found until patients self-report symptoms or they become radiologically evident. We have developed an engineered metastatic niche (scaffold) that recruits aggressive tumor cells prior to their colonization in other organs. The engineered niche can be monitored for dynamic gene expression, and changes at this site are analogous to those in a native metastatic site (lung) for triple negative breast cancer (4T1 cells). We were able to develop a 10-gene signature from the scaffold that accurately monitors disease progression and recurrence or resistance to resection therapy. This data set acts to dissect the heterogeneity of the cell populations in the engineered and native metastatic niche and identify the cell types that contribute to the success of the signature.
2022-08-02 | E-MTAB-8503 | biostudies-arrayexpress