Gene expression profile at single cell level of cells from subcutaneous implanted syngeneic fibrosarcoma tumors in C57BL/6 mice injected with autologous erythrocytes suspended in buffered saline
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE268581 | GEO | 2024/08/30
REPOSITORIES: GEO
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Project description:Iron-rich tumor-associated macrophages (iTAMs) are characterized by high intracellular iron, heme metabolism, and expression of the endothelin receptor B. iTAMs promote angiogenesis and immunosuppression in tumors. Heme-mediated degradation of the transcriptional repressor BACH1 induces the iTAM transcriptional program in macrophages.
2024-08-30 | GSE269203 | GEO
Project description:Aging affects iron homeostasis and erythropoiesis, as evidenced by tissue iron loading in rodents and common anemia in the elderly. Given thatred pulp macrophages (RPMs) continuously process iron, their cellular functions might be susceptible to age-dependent decline, affecting organismal iron metabolism and red blood cell (RBCs) parameters. However, little is known about the effects of aging on the functioning of RPMs. To study aging RPMs, we employed 10-11-months-old female mice that show serum iron deficiency and iron overload primarily in spleens compared to young controls. We observed that this is associated with iron loading, oxidative stress, diminished lysosomal activity, and decreased erythrophagocytosis rate in RPMs. We uncovered that these impairments of RPMs lead to the retention of senescent RBCs in the spleen, their excessive local hemolysis, and the formation of iron- and heme-rich large extracellular protein aggregates, likely derived from damaged ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation and reactive oxygen species build-up in RPMs, improves their ability to clear and degrade erythrocytes, and limits ferroptosis. Consequently, this diet improves splenic RBCs fitness, limits hemolysis and the formation of iron-rich protein aggregates, and increases serum iron availability in aging mice. Using RPM-like cells, we show that diminished erythrophagocytic and lysosomal activities of RPMs can be attributed to a combination of increased iron levels and reduced expression of heme-catabolizing enzyme heme oxygenase 1 (HO-1). Taken together, we identified RPM dysfunction as an early hallmark of physiological aging and demonstrated that dietary iron reduction improves iron turnover efficacy.
2023-01-31 | GSE199879 | GEO
Project description:Both iron homeostasis and erythropoiesis are known to be affected by aging. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by red pulp macrophages (RPMs) in the spleen. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. In our project, we identified a formation of undegradable iron- and heme-rich extracellular aggregates in the spleens of 10-11-month-old female mice. We further found that feeding mice an iron-reduced diet alleviates the deposition of iron in the spleen in the form of these insoluble aggregates. Here, we performed: i) label-free proteomic analysis of the aggregates that were magnetically isolated from the aged mice (maintained on a standard diet), using samples from young mice as a background control; and ii) TMT-based quantification of the differences in the aggregate protein composition between mice that aged on a standard versus iron-reduced diet. In each experiment, three biological replicates per group were analyzed.
2023-02-02 | PXD032900 | Pride
Project description:Macrophages are central in regulating iron homeostasis. Transcription repressor Bach1 regulates by heme. Here we investigated the relationship between heme-regulated Bach1 and bone marrow derived macrophage. We found that Bach1 KO macrophage showed that up-regulated genes were the process that iron-heme homeostasis and maintenance related gene compared with WT. Our results suggest that Bach1 expression is important to the heme homeostasis and maintenance in the bone marrow derived macrophage.
2019-03-30 | GSE79717 | GEO
Project description:Macrophages are central in regulating iron homeostasis. Transcription repressor Bach2 regulates by heme. Here we investigated the relationship between heme-regulated Bach2 and macrophage in bone marrow. We identified RFP-positive and negative macrophage were in bone marrow. We found that RFP-positive macrophage related with iron-heme homeostasis maintenance and RPF-negative population related with immune response. In RFP positive macrophage, we also found the lysosomal heme transporter hrg-1 was Bach2 direct target gene. Our results suggest that the function of the bone marrow macrophage alters according to expression of Bach2.
2018-09-26 | GSE79697 | GEO
Project description:Background. Animal models of elastase intratracheal instillation have shown that elastase, unopposed by α-1 antitrypsin (AAT), can induce alveolar hemorrhage with ensuing macrophage inflammation and lung damage. Aim. To identify markers of alveolar hemorrhage and damage using bronchoalveolar lavage (BAL) samples and lung tissue explants from AAT deficient (AATD) subjects. Methods. BAL samples (17 patients, 15 controls) were evaluated for free heme and iron concentrations. Alveolar macrophage (AlvMac) activation patterns were assessed by RNA sequencing and validated in vitro using heme-stimulated monocyte-derived macrophages (MDM). Lung explants (7 patients, 4 controls) were evaluated for iron sequestration patterns, by Prussian blue stain and ferritin immunohistochemistry, and for ferritin iron imaging and elemental analysis by electron microscopy (EM). Tissue oxidative damage was assessed by 8-OHdG immunohistochemistry. Results. BAL showed significantly elevated free heme and iron concentrations at lobar level. BAL macrophage RNA sequencing showed innate proinflammatory activation, consistent with free heme activation. AATD tissue alveolar and interstitial macrophages showed elevated iron and ferritin accumulation in large lysosomes packed with iron oxide cores with degraded ferritin protein cages. AATD explants showed massive oxidative DNA damage in lung epithelial cells and macrophages. Conclusions. Identification of BAL and tissue markers of alveolar hemorrhage, together with the molecular and cellular evidence of macrophage innate pro-inflammatory activation and oxidative damage, consistent with free heme stimulation, provides ex vivo evidence for the pathogenetic role of elastase-induced alveolar hemorrhage AATD emphysema as shown in animal studies.
2023-04-25 | GSE194313 | GEO
Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Bone marrow derived macrophages were generated in vitro by culturing WT and Bach1 knock out bone marrow in the presence of GM-CSF and their global gene expression pattern were compared in the presence or absence of heme at the various indicated time points after treatment. GMP and MPP populations were sorted from fetal liver chimeras and pooled by donor genotype. RNA was isolated using an RNAqueous-Micro Kit (Ambion) and submitted for amplification, labeling and hybridization. Expression values were analyzed after RMA quantile normalization using ArrayStar software (DNASTAR).
2014-03-14 | E-GEOD-53796 | biostudies-arrayexpress
Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Global gene expression pattern of bone marrow-derived macrophages generated with GM-CSF in vitro and treated with heme were compared to those treated with vehicle at 6 hours, 24 hours, and 72 hours after treatment. GM-CSF cultures of Spic(igfp/igfp) BM cells were treated with heme (80 µm) or vehicle after 6 days in culture. Adherent fraction of cells were harvested 6 hours, 24 hours, and 72 hours after treatment and RNA was isolated using an RNeasy mini kit (Qiagen) and submitted for amplification, labeling and hybridization. Expression values were analyzed after RMA quantile normalization using ArrayStar software (DNASTAR).
2014-03-14 | E-GEOD-46983 | biostudies-arrayexpress
Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Global gene expression pattern of bone marrow-derived macrophages generated with GM-CSF in vitro and treated with heme were compared to those treated with vehicle at 6 hours, 24 hours, and 72 hours after treatment.
2014-03-14 | GSE46983 | GEO
Project description:We used bulk RNA sequencing to study the differences between iron-high and iron-low tumor associated macrophages in murine fibrosarcoma.
2024-08-30 | GSE269437 | GEO