Cancer coopts differentiation of B-cell precursors into macrophages [mouse]
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ABSTRACT:
PROVIDER: PRJNA747690 | ENA |
REPOSITORIES: ENA
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Project description:We recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancer cells also coopt differentiation of the extranodal B-cell precursors to generate macrophages (termed B-MF). We link the trans-differentiation to a small subset of CSF1R+ Pax5Lo cells within BM pro-/pre-B and immature B cells and cancer-secreted M-CSF that downregulates Pax5 via CSF1R signaling. Thus, cancer generates tumor-associated macrophages (TAM) from B-cell precursors besides their primary source, monocytes. Based on their differences from monocyte-derived TAM, such as a superb ability to induce FoxP3+ Tregs, suppress proliferation of T cells and more efficiently phagocytize apoptotic cells, we propose that cancer generates B-MF to mediate cancer escape.
2021-09-20 | GSE180283 | GEO
Project description:Cancer coopts differentiation of B-cell precursors into macrophages
| PRJNA747688 | ENA
Project description:Cancer coopts differentiation of B-cell precursors into macrophages [human]
| PRJNA747692 | ENA
Project description:We recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancer cells also coopt differentiation of the extranodal B-cell precursors to generate macrophages (termed B-MF). We link the trans-differentiation to a small subset of CSF1R+ Pax5Lo cells within BM pro-/pre-B and immature B cells and cancer-secreted M-CSF that downregulates Pax5 via CSF1R signaling. Thus, cancer generates tumor-associated macrophages (TAM) from B-cell precursors besides their primary source, monocytes. Based on their differences from monocyte-derived TAM, such as a superb ability to induce FoxP3+ Tregs, suppress proliferation of T cells and more efficiently phagocytize apoptotic cells, we propose that cancer generates B-MF to mediate cancer escape.
2021-09-20 | GSE180284 | GEO
Project description:In response to the cytokines, macrophage colony-stimulating factor and receptor activator of NF-kB ligand, monocyte precursors differentiate into bone marrow-derived macrophages (BMDMs) that ultimately fuse to form multi-nucleated osteoclasts, following a tightly controlled genetic program where specific sets of genes are differentially expressed. We used microarrays to examine the gene expression profile underlying mouse osteoclast differentiation.
2019-10-03 | GSE138324 | GEO
Project description:Cancer actively uses B cells to promote its progression and metastasis. For example, it causes accumulation of bone marrow (BM) B-cell precursors in spleen to convert into immunosuppressive Breg cells. Here, we provide evidence that cancer also coopts differentiation BM CSF1R+ Pax5Lo B-cell precursors to generate macrophages (termed B-MF cells). To do this, cancer uses CSF1 to trigger Csf1r signaling and downregulate PAX5 in B-cell precursors by activating FOXO1. Although tumor-associated macrophages (TAMs) are primarily derived from BM monocytes, our data suggest that some of them may have B-cell origin. Unlike monocyte-derived TAMs, B-MF exhibit a higher M2 polarization, more efficiently phagocytize apoptotic cells, induce FoxP3+ Tregs and suppress T cells activity. We propose that the cancer-B-MF axis is a novel immune escape pathway, thus a therapeutic target.
2021-09-20 | GSE178716 | GEO
Project description:<p>Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. <em>In vitro</em> macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1-and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM-and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for <em>in vitro</em> macrophage studies. </p>
2023-09-19 | MTBLS6502 | MetaboLights
Project description:All established protocols for differentiation of mouse and human pluripotent stem cells into specific neural subpopulations generate a considerable cellular heterogeneity that hampers experimental and clinical progress. In order to obtain a homogenous population of neuronal precursor cells and to streamline the differentiation of embryonic stem cells (ESCs), we assessed PSA-NCAM, a surface glycoprotein that is specifically expressed on immature neurons. We developed an optimized strategy for magnetic isolation of PSA-NCAM positive neuronal precursors from differentiated ESC cultures and characterized their neuronal differentiation potential in vitro. PSA-NCAM enrichment at an early step of neural differentiation increased the number of ES cell derived neurons and reduced cellular diversity. Gene expression analysis revealed that mainly genes involved in neuronal activity were over-represented after purification. The in vivo potential of in vitro derived PSA-NCAM+ enriched precursors was functionally characterized by grafting into the forebrain of adult mice. Analysis for several neuronal and glia markers at 10 or 40 days post graft showed a distinct differentiation pattern. While unsorted control cells gave rise to a mixed population composed of immature precursors, early postmitotic neurons or glial cells, the majority of PSA-NCAM+ enriched cells differentiated into NeuN positive neurons. Furthermore, when in contact with the rostral migratory stream, higher numbers of cells integrated into the stream and migrated towards the olfactory bulb when the PSA-NCAM enriched population was grafted. Thus, enrichment of neuronal precursors based on PSA-NCAM expression represents a general and straightforward approach to narrow cellular heterogeneity during neuronal differentiation of pluripotent cells. Two conditions (step 4, step 5), each represented by three biological replicates of control and enriched cells (Cy5); mESC was used as common reference (Cy3)
2013-12-21 | E-GEOD-35125 | biostudies-arrayexpress
Project description:A major population of placenta macrophages represented throughout the pregnancy consists of CD14+ macrophages, but their characteristics remain badly understood. Here we purified from placentas at term CD14+ macrophages using positive selection. The phenotyping of CD14+ macrophages performed using flow cytometry revealed that placenta CD14+ macrophages expressed a series of markers distinct of those of circulating monocytes monocyte-derived macrophages. Placenta CD14+ macrophages spontaneously matured in multinucleated giant cells (MGCs) as demonstrated by size, number of nuclei display and specific cytoskeleton organization. Placenta CD14+ macrophages and MGCs were phagocytic cells but the potential of MGCs to mount an inflammatory response was lower than that of their precursors. Placenta CD14+ macrophages and MGCs stimulated with interferon and interleukin-4 were not polarized into typical M1 or M2 profiles. Placenta macrophages exhibited specific activation transcriptional programs. Indeed, principal component analysis and hierarchical clustering show that placental macrophages formed a distinct group from circulating monocytes and monocyte-derived macrophages. Among placenta macrophages, it was also possible to distinguish CD14+ macrophages and MGCs. In addition, networks based on gene interactions were clearly different in CD14+ macrophages and MGCs. Finally, the microenvironment of placenta CD14+ macrophages governs their differentiation into MGCs because CD14+ macrophages incubated with trophoblasts exhibited exarcerbated characteristics of MGCs and because the co-incubation of circulating monocytes from working women with trophoblast supernatants resulted into the formation of MGCs whereas monocytes from non-pregnant women incubated with trophoblast supernatants did not differentiate into MGCs. Taken together, these results clearly demonstrated specific feaures of placenta CD14+ macrophages. Three replicates of each of the following: 1. Placental macrophages just after isolation (CD14+ macrophages) 2. Placental macrophages after 9 days in culture (MGCs) 3. CD14+ cells isolated from PBMC which are extracted from the whole human blood of healthy donors (Monocytes) 4. Macrophages derived from monocytes (MDMs)
2012-12-07 | E-GEOD-29575 | biostudies-arrayexpress
Project description:All established protocols for differentiation of mouse and human pluripotent stem cells into specific neural subpopulations generate a considerable cellular heterogeneity that hampers experimental and clinical progress. In order to obtain a homogenous population of neuronal precursor cells and to streamline the differentiation of embryonic stem cells (ESCs), we assessed PSA-NCAM, a surface glycoprotein that is specifically expressed on immature neurons. We developed an optimized strategy for magnetic isolation of PSA-NCAM positive neuronal precursors from differentiated ESC cultures and characterized their neuronal differentiation potential in vitro. PSA-NCAM enrichment at an early step of neural differentiation increased the number of ES cell derived neurons and reduced cellular diversity. Gene expression analysis revealed that mainly genes involved in neuronal activity were over-represented after purification. The in vivo potential of in vitro derived PSA-NCAM+ enriched precursors was functionally characterized by grafting into the forebrain of adult mice. Analysis for several neuronal and glia markers at 10 or 40 days post graft showed a distinct differentiation pattern. While unsorted control cells gave rise to a mixed population composed of immature precursors, early postmitotic neurons or glial cells, the majority of PSA-NCAM+ enriched cells differentiated into NeuN positive neurons. Furthermore, when in contact with the rostral migratory stream, higher numbers of cells integrated into the stream and migrated towards the olfactory bulb when the PSA-NCAM enriched population was grafted. Thus, enrichment of neuronal precursors based on PSA-NCAM expression represents a general and straightforward approach to narrow cellular heterogeneity during neuronal differentiation of pluripotent cells.
2013-12-21 | GSE35125 | GEO