Malaria pigment hemozoin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA929988 | ENA |
REPOSITORIES: ENA
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Project description:The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin. The genes modulated by TNF-alpha were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin increases expression of transcription factors that form part of the integrated stress response which is accompanied by reduced expression of genes involved in DNA repair. This study confirms that hemozoin induces cellular stress on erythroblasts that is additional to and distinct from responses to inflammatory cytokines and identifies new genes that may be involved in the pathogenesis of severe malarial anemia. More generally the respective transcription profiles highlight the varied mechanisms through which erythropoiesis may be disrupted during infectious disease. Erythroblasts derived from PBMCs were enriched to 97% purity for proerythroblast and intermediate/normoblast phases of differentiation using magnetic bead isolation. There were three treatment groups: media, P.falciparum hemozoin (12.5 microgram /ml hematin units) and tumour necrosis factor alpha(10ng/ml). Total RNA using 7.5 x105 cells per treatment from one donor was extracted using Trizol. Highly significant gene ontological findings (where p> x10^-17 but < x10^-7) were confirmed by quantitative PCR.
2015-02-04 | E-GEOD-65577 | biostudies-arrayexpress
Project description:The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin. The genes modulated by TNF-alpha were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin increases expression of transcription factors that form part of the integrated stress response which is accompanied by reduced expression of genes involved in DNA repair. This study confirms that hemozoin induces cellular stress on erythroblasts that is additional to and distinct from responses to inflammatory cytokines and identifies new genes that may be involved in the pathogenesis of severe malarial anemia. More generally the respective transcription profiles highlight the varied mechanisms through which erythropoiesis may be disrupted during infectious disease.
2015-02-04 | GSE65577 | GEO
Project description:Malaria pigment hemozoin-induced transcriptional remodeling of mouse hematopoietic stem and progenitor cells, granulocyte-macrophage progenitors, and bone marrow monocytes
| PRJNA929995 | ENA
Project description:Malaria pigment hemozoin-induced chromatin remodeling of mouse hematopoietic stem and progenitor cells, granulocyte-macrophage progenitors, and bone marrow monocytes
| PRJNA929994 | ENA
Project description:Malaria in pregnancy remains a substantial public health concern in malaria-endemic areas. Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes (IE) in the placental intervillous blood spaces have been associated to poor neonatal outcomes, including low birth weight due to fetal growth restriction. However, little is known about the molecular changes occurring in the placenta in past-stages of P. falciparum infection when the hemozoin pigment is present in the absence of parasites. We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in P. falciparum infected and non-infected placentas aiming to find molecular changes occurring in past-stage infection. A total of 2946 proteins, 1733 glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis, as well as AKT and ERK signaling pathways activation, which together with clinical data and literature-based information were further correlated to an increased apoptosis in infected placentas. This study showed apoptosis-related mechanisms associated with past-stage of malaria infection that can be further explored as therapeutic target against adverse pregnancy outcomes in placental malaria.
2018-09-25 | PXD008079 | Pride
Project description:Plasmodium falciparum parasites have a complex life cycle, but the most clinically relevant stage of the disease is the invasion of erythrocytes and the proliferation of the parasite in the blood. The influence of human genetic traits on malaria has been known for a long time, however understanding the role of the proteins involved is hampered by the anuclear nature of erythrocytes that makes them inaccessible to genetic tools. Here we overcome this limitation with a differentiation protocol to derive erythroid cells in vitro from a diversity of human stem cells and an adaptation of flow cytometry to detect hemozoin. We combine this strategy with genome editing to show that deletion of basigin ablates invasion while deletion of ATP2B4 has a minor effect and that erythroid cells from reprogrammed patient-derived HbBart αthalassemia samples poorly support infection. This approach offers vast potential for understanding the impact human polymorphisms on malaria.
2023-10-21 | GSE245735 | GEO
Project description:Retinal pigment epithelial cells are critical for eye function and loss of cell function is linked to age-related blindness. Relatively little is known about the transcriptional regulatory networks in these cells. The datasets presented here are ChIP-seq experiments for RNA polymerase II , transcription factors and histone modifications in human retinal pigment epithelial cells. ChIP-Seq for transcription factors, RNA polymerase, histone modifications and CTCF in retinal pigment epithelial cells
2014-08-03 | E-GEOD-60024 | biostudies-arrayexpress
Project description:In zebrafish, there are interactions between black pigment cells (melanophores) and yellow pigment cells (xanthophores) for pigment-pattern formation. However, the detailed molecular mechanism of these interactions remains largely unknown. We used microarray for identifying the molecular basis of these interactions by comparing gene expression between melanophores and xanthophores. Zebrafish pigment cells were collected from adult-fish fins by centrifugal separation or using cell sorter. melanophores vs. xanthophores
2013-05-30 | E-GEOD-42129 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-08 | GSE224162 | GEO
Project description:In zebrafish, there are interactions between black pigment cells (melanophores) and yellow pigment cells (xanthophores) for pigment-pattern formation. However, the detailed molecular mechanism of these interactions remains largely unknown. We used microarray for identifying the molecular basis of these interactions by comparing gene expression between melanophores and xanthophores.
2013-05-30 | GSE42129 | GEO