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
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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: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
| PRJNA1117843 | ENA
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:Haemophilus influenzae frequently causes human disease, and humans are it’s sole niche. This bacterium has an absolute requirement for both a porphyrin and an iron source for aerobic growth, and exogenous heme can satisfy both requirements. Heme and iron can be acquired by H. influenzae from free or human protein-bound sources. The ability to selectively regulate the acquisition of heme and iron from physiological sources is a major virulence determinant for this microorganism. We utilized whole genome arrays to identify the full set of H. influenzae Rd KW20 iron and heme regulated genes. Condition specific RNA was derived from cells starved for both heme and iron and cells from the same culture 20 mins after the addition of exogenous iron and heme. The results identified 162 genes with a change in transcription ≥ 1.5 fold. Eighty genes in 42 operons were preferentially expressed under iron/ heme starvation; 82 genes in 50 operons were preferentially expressed under iron/heme replete conditions. In each case, all genes contained within the operon were co-regulated. The former group included genes encoding proteins known to have a role in iron and heme uptake as well as several hypothetical ORFs. Enzymes involved in the gluconeogenesis pathway and glycogen biosynthesis were also upregulated. The genes showing increased transcription immediately after the addition of iron and heme primarily encode proteins involved with aerobic respiration and protein biosynthesis, consistent with a relaxation of starvation. Genomic transcriptional profiling provides a more complete understanding of the effects of iron and heme availability. Keywords: Transcription analyses
2006-07-28 | GSE5061 | GEO
Project description:Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1–/– mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin.
2016-12-14 | GSE78955 | GEO
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. Keywords: Transcription analyses Three replicate cultures were grown in iron and heme depleted media for 90 minutes and samples taken for expression analyses. Fe and heme were supplemented to the remaining cultures and the cultures allowed to incubate an additional 20 minutes. Microarray analyses were used to determine changes in gene expression resulting from transfer from FeHm-deplete to FeHm-replete conditions.
2009-01-20 | E-GEOD-11349 | biostudies-arrayexpress
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. Keywords: Transcription analyses Three replicate cultures were grown in iron and heme depleted media for 90 minutes and samples taken for expression analyses. Fe and heme were supplemented to the remaining cultures and the cultures allowed to incubate an additional 20 minutes. Microarray analyses were used to determine changes in gene expression resulting from transfer from FeHm-deplete to FeHm-replete conditions.
2009-01-20 | E-GEOD-11354 | biostudies-arrayexpress
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. Keywords: Transcription analyses
2009-01-21 | GSE11354 | GEO
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. This SuperSeries is composed of the SubSeries listed below.
2009-01-21 | GSE11362 | GEO