Project description:How erythropoiesis responds to fasting remains to be explored. Here, Xu et al. showed that short-term intensive fasting promotes the production of red blood cells and boosts their functions by regulating MS4A3-CDK2 module to enhance megakaryocyte-erythroid progenitor self-renewal and erythroid-biased differentiation.
Project description:Caloric restriction is considered to be anti-inflammatory. In this study we examined the effect of fasting on peripheral leukocyte populations. We found that short-term fasting affects metabolic and pro-inflammatory activity of monocytes and decreases numbers of circulating monocytes. For this study, we sorted hepatocytes from fed and fasted mice, monocytes from bone marrow from fed and fasted mice, and monocytes from bone marrow from wildtype and Ccr2-deficient mice.
Project description:Erythropoiesis takes place mostly in bone marrow and ends in blood. Previous studies have shown that hypoxia has direct effects on the bone marrow, which could promotes erythropoiesis by modulating erythroid progenitor maturation. However, how bone marrow microenvironment participates in erythropoiesis under hypoxia still need further clarification. In this study, we analyzed transcriptional changes of bone marrow cells of mice exposed to 5000 m altitude hypoxia for 1 week. We profiled the top 20 up-regulated secreted factor genes after treatment with hypoxia, and found TFPI was one of the secreted factor genes with the highest expression.
Project description:Human studies of Plasmodium vivax in the bone marrow are scarce. Here, we present a detailed characterization of bone marrow aspirates taken from a P. vivax patient with high parasitaemia on admission and 42 days after treatment. Analysis of miRNAs related to erythropoiesis revealed a distinct series of differentially expressed miRNAs during infection compared to at convalescence. These results suggest that parasites in the bone marrow affect erythropoiesis.
Project description:Short-term fasting elicits beneficial effects in mice and humans, including protection from chemotherapy toxicity, but the involved mechanisms are not well understood. We collected blood samples from healthy human volunteers and mice before and after 36 or 24 hours of fasting, respectively, to measure fatty acid composition of erythrocyte membranes, circulating miRNAs, and RNA expression at PBMCs. In both mice and humans, fasting affected the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane. Also, fasting significantly reduced the expression at PBMCs of insulin signaling-related genes, including the SREBP lipid-metabolizing pathway, in correlation with changes in membrane fatty acids. We tested the relevance of these fatty acid homeostasis parameters using a complete platform to monitor chemotherapy toxicity in mice. When fasted for 24 hours before and 24 hours after administration of the chemotherapeutic drug oxaliplatin, mice showed a strong protection from kidney, liver, heart and bone marrow toxicity. Importantly, the newly discovered fasting parameters defined two clearly separated groups of individuals that accurately predicted a differential protection from chemotherapy toxicity. Our results reveal a novel mechanism of fasting associated with fatty acids homeostasis, and provide novel biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.
2022-06-12 | GSE173241 | GEO
Project description:Chronic stress induced bone marrow immunosuppressive erythropoiesis
Project description:Murine long-term hematopoietic stem cells (HSCs), short-term HSCs and multipotent progenitor cells (MPPs) were isolated from bone marrow and expression profiled on Affy chips. The behavior of maternal-specific imprinting genes, particularly in the H19-Igf2 locus, was focused on, to see if any might be involved in maintaining quiescence of long-term stem cells.
Project description:The unique properties of the bone marrow allow for migration and proliferation of multipl myeloma (MM) cells, while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. Bone marrow adipocytes (BMAds), which have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary bone marrow cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes derived by differentiating bone marrow-derived mesenchymal stromal cells (MSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, they likely will recapitulate in vivo biology better than MSC-derived adipocyte, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd may not be the same as the MSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing primary BMAds (pBMAds): 2D coverslips, 2D transwells, and 3D silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the bone marrow microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human bone marrow. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for short term (~2 weeks) or long term (1 month) in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In sum, we developed three in vitro cell culture systems to study primary bone marrow adipocytes and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the bone marrow, including other bone-homing tumor types.