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TFPI from Erythroblasts Drives Heme Production in Central Macrophages Promoting Erythropoiesis in Polycythemia Vera

ABSTRACT: TFPI from Erythroblasts Drives Heme Production in Central Macrophages Promoting Erythropoiesis in Polycythemia Vera

PROVIDER: PRJNA933340 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23388144_1.fastq.gz	Fastqsanger.gz
	SRR23388144_2.fastq.gz	Fastqsanger.gz
	SRR23388145_1.fastq.gz	Fastqsanger.gz
	SRR23388145_2.fastq.gz	Fastqsanger.gz
	SRR23388146_1.fastq.gz	Fastqsanger.gz

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TFPI from Erythroblasts Drives Heme Production in Central Macrophages Promoting Erythropoiesis in Polycythemia Vera

Project description:Erythropoietic homeostasis is coordinated by erythroblast development and challenged by a number of genetic diseases including polycythemia vera. Erythroblasts and central macrophages form erythroblastic islands to provide a specific environment for erythropoiesis. However, how central macrophages interplay with erythroblasts during erythropoiesis remains to be further clarified. In this study, we found that erythroid-specific TFPI knockout decreased the number of erythroblasts under both steady-state and stress conditions, and the function of TFPI in erythropoiesis was mediated by macrophages. TFPI affects the downstream heme synthesis pathway of central macrophages, as shown by RNA sequencing analysis, and the deletion of TFPI reduced the heme content of macrophages by inhibiting ferrochelatase (Fech) expression. Our results show that TFPI plays an important role in the regulation of erythropoiesis and reveal a new mechanism of interplay between erythroblasts and macrophages. TFPI will also provide a new potential treatment strategy for polycythemia vera.

2024-03-01 | GSE224994 | GEO

Transcriptional profiling of normal and JAK2V617F-positive erythroblasts of polycythemia vera and essential thrombocythemia

Project description:This experiment was designed to identify genes differentially expressed in association with the JAK2V617F mutation in polycythemia vera (PV) and essential thrombocythemia (ET). Peripheral blood was obtained from 20 ET and 16 PV patients and erythroid progenitors were grown in semi-solid methylcellulose media supplemented with 0.01 U/ml erythropoietin. Individual clones were plucked and genotyped for the presence of the JAK2V617F mutation, and up to 20 normal and mutant colonies were pooled from each patient, and subjected to expression profiling. In total, 72 expression profiling datasets were generated, representing paired samples of normal and mutant cells from 36 patients.

2011-11-22 | E-MTAB-384 | biostudies-arrayexpress

Quantitative Analysis of the erythrocyte membrane proteins in polycythemia vera patients treated with hydroxycarbamide

Project description:Polycythemia vera (PV) is a myeloproliferative disorder arising in pluripotent stem cells that causes an abnormal erythrocyte mass. More than 90% of PV patients have a mutation in JAK2 protein that is closely associated with the erythrocyte membrane. We report findings on quantitative analysis of the erythrocyte membrane proteins differentially regulated in PV patients treated with hydroxycarbamide.</br>Kottahachchi et al., EuPA Open Proteomics 7, 43-53</br>Quantitative analysis of the erythrocyte membrane proteins in polycythemia vera patients treated with hydroxycarbamide</br>DOI:10.1016/j.euprot.2015.04.001</br><a href="http://www.sciencedirect.com/science/article/pii/S2212968515000100">http://www.sciencedirect.com/science/article/pii/S2212968515000100</a>

2015-05-11 | PXD001532 | Pride

Iron and Heme Coordinate Erythropoiesis through HRI-Mediated Regulation of Protein Translation and Gene Expression

Project description:Iron and heme play central roles in red blood cell production. However, the mechanisms by which iron and heme levels coordinate erythropoiesis remain incompletely understood. HRI is a heme-regulated kinase that controls translation by phosphorylating eIF2a. Here, we investigate the global impact of iron, heme and HRI on protein translation in vivo in murine primary erythroblasts using ribosome profiling. By defining the underlying changes in translation during iron and HRI deficiencies, we validate known regulators of this process, including Atf4, and identify novel pathways such as co-regulation of ribosomal protein mRNA translation. Surprisingly, we found that heme and HRI pathways, but not iron-regulated pathways, mediate the major protein translational and transcriptional responses to iron deficiency in erythroblasts in vivo and thereby identify previously unappreciated regulators of erythropoiesis. Our genome-wide study uncovers the major impact of the HRI-mediated integrated stress response for the adaptation to iron deficiency anemia.

2018-09-03 | GSE119365 | GEO

Investigating the proteome of red blood cells and reticulocytes in Polycythemia Vera and Essential Thrombocythemia

Project description:The project aims at comparing the effect of the JAK2V617F mutation on protein expression in human erythroid cells in the context of Polycythemia Vera and Essential Thrombocythemia

2022-02-17 | PXD029965 | Pride

Expression data from murine splenic erythroblasts in stress erythropoiesis.

Project description:In absence of selenium, proerythroblasts exhibited delay in differentation into basophilic erythroblasts during phenylhydrazine induced stress erythropoiesis. This microarray project was aiming to explore gene expression patterns in erythroblasts in the function of selenium status.

2018-05-28 | GSE102056 | GEO

Changes of miRNA expression in granulocytes of patients with polycythemia vera (PV) and essential thrombocythemia (ET) receiving INCB018424 in a Phase 2 study

Project description:A global microRNA expression profile was obtained from gradient-purified granulocytes (>95% pure) collected at the time of screening and at cycle 4 of treatment Protocol #18424-256 is a Phase 2 study of the JAK1 and JAK2 inhibitor INCB01842 in patients with advanced polycythemia vera (PV) and essential thrombocythemia (ET) refractory to hydroxyurea;

2012-09-26 | GSE32194 | GEO

Gene Expression Profiling in Polycythemia Vera (PV)

Project description:To define the molecular abnormalities at the stem cell level in polycythemia vera (PV), we examined global gene expression in circulating CD34+ cells from 19 JAK2 V617F-positive PV patients and 6 normal individuals using Affymetrix oligonucleotide microarray technology. We observed that CD34+ cell gene expression not only differed between the PV patients and the normal controls but also between men and women PV patients. Based on these gender-specific differences in gene expression, we were able to identify 102 genes differentially regulated concordantly by both men and women, which likely represent a core set of genes whose dysregulation is involved in the pathogenesis of PV. Gene expression was verified by Q-PCR of patient CD34+ cell RNA. Using the 102 gene set and unsupervised hierarchical clustering, the 19 PV patients could be separated in two groups that differed significantly with respect to hemoglobin level, thrombosis frequency, splenomegaly, splenectomy or chemotherapy exposure, leukemic transformation and overall survival. These results were confirmed using top scoring pairs, which identified a different set of 29 genes that independently segregated the 19 patients into the same two clinical groups: those with an aggressive form of the disease (7 patients), and those with an indolent form (12 patients).

2014-08-29 | GSE47018 | GEO

Gene Expression Profiling in Polycythemia Vera (PV)

2014-08-29 | E-GEOD-47018 | biostudies-arrayexpress

Proteome in human hematopoietic stem and progenitor cell subpopulations from polycythemia vera patients and controls

Project description:Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by hyper-proliferation of the erythroid, megakaryocytic and granulocytic lineages and the presence of an activating mutation in JAK2. To elucidate mechanisms that regulate PV stem cells, we applied a newly developed data-independent acquisition (DIA) mass spectrometry (MS) technology to purified hematopoietic stem and progenitor cell (HSPC) subpopulations of patients with chronic and progressed PV. Proteomic analyses were supplemented by RNA-sequencing (RNA-seq) and identified targets validated by flow cytometry and functional in vitro assays.

2022-01-19 | PXD021178 | Pride

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