Developmental differences between neonatal and adult human erythropoiesis
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PROVIDER: PRJNA419347 | ENA |
REPOSITORIES: ENA
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Project description:Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood- and peripheral blood-HSPC induced towards erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC and differentiated them in vitro. We observed that cells derived from cord blood proliferate 4.5 times more than cells derived from peripheral blood. However, these cells present a delay in their differentiation pattern due to increased quantities of progenitors, notably CFU-E. Using our method of immunophenotyping for the study of erythroid progenitors, we document the presence and maintenance of a specific population in peripheral blood-derived erythroid progenitors. This population, defined as IL3R-GPA-CD34+CD36+, has the ability to form both BFU-E and CFU-E colonies in colony-forming assays, reflecting a higher potential. To further understand the differences between cord blood- and peripheral blood- HSPC, we sorted all stages of erythropoiesis from both sources and compared their transcriptome. We document differences at the CD34, BFU-E, poly- and orthochromatic stages. Among the genes presenting the highest differences in expression, many are involved in the regulation of the cell cycle and autophagy. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis and highlight functional differences, critical to our understanding of the impact of the developmental origin of HSPCs on erythroid differentiation.
2017-12-28 | GSE107218 | GEO
Project description: Not available
| S-EPMC5842122 | biostudies-literature
Project description:We study the role of glycosylation in ion channel function. Specfically, we are focusing on how ion channel glycosylation modulates, controls, and impacts cardiac, skeletal muscle, and neuronal electrical activity. We wish to determine differences in gene expression through development and between the atria and ventricles of the mouse heart. Our data indicate differential sialylation directly affects voltage-gated sodium channel function through the developing heart in a chamber-specific manner. We wish to expand our findings to include other ion channels involved in the cardiac action potential, and to eventually create a map of the cardiac conduction system that details the role of differential glycosylation in cardiac excitability. Determining differential expression of the genes that regulate ion channel glycosylation is vital to these goals. We analyzed four sets of pooled RNA to be run in triplicate: one each from neonatal and adult mouse atria and ventricles.
2011-03-02 | E-GEOD-27589 | biostudies-arrayexpress
Project description:It has been proposed that developmental differences exist between neonatal and adult platelets. Detailed insight therein is, however, still lacking. We have now compared the platelet protein expression profile of neonates and adults employing a label-free quantitative mass spectrometry approach. In addition, platelet aggregation mediated by thromboxane A2 analog, collagen, and peptide agonists of the protease-activated-receptors 1 and 4 was assessed. Results showed that neonatal platelets effectively aggregate in the presence the employed platelet agonists. In agreement with previous studies, higher concentrations of the agonists were required to initiate aggregation in the neonatal platelets. Mass spectrometry analysis revealed no significant difference in the expression level of critical adhesive platelet proteins like glycoprotein (GP)Ib, integrin αIIbβ3, GPV and GPIX. Neonatal platelets did show reduced expression levels of proteins involved in intracellular signaling, i.e. LYN, MAP3k5 and FAM129A. Several proteins that are known to be related to mitochondrial energy metabolism processes such as oxidative phosphorylation, i.e. NDUFS3, NDUFS8 and NDUFA1 were upregulated in neonates. In conclusion, this study reveals that the platelets derived from neonates and adults are distinct. In particular, developmental changes were observed for proteins that belong to metabolic and energy generation processes.
2021-02-05 | PXD004578 | Pride
Project description:We study the role of glycosylation in ion channel function. Specfically, we are focusing on how ion channel glycosylation modulates, controls, and impacts cardiac, skeletal muscle, and neuronal electrical activity. We wish to determine differences in gene expression through development and between the atria and ventricles of the mouse heart. Our data indicate differential sialylation directly affects voltage-gated sodium channel function through the developing heart in a chamber-specific manner. We wish to expand our findings to include other ion channels involved in the cardiac action potential, and to eventually create a map of the cardiac conduction system that details the role of differential glycosylation in cardiac excitability. Determining differential expression of the genes that regulate ion channel glycosylation is vital to these goals.
2011-03-02 | GSE27589 | GEO
Project description:Comparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.
2005-10-01 | E-MEXP-354 | biostudies-arrayexpress
Project description:We report the comparative investigation of genome-wide chromatin state maps, transcription factor (TF) occupancy, and gene expression profiles from developing red cell precursors at two developmental stages. Contrasting the similarities and differences between fetal and adult erythropoiesis provides important insights into the erythroid gene expression programs and gene regulatory networks. Specifically, comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that master regulators, such as GATA1 and TAL1, cooperatively act within active enhancers but have little predictive value for stage-specific enhancer activity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of adult-stage expression program. Thus, the combinatorial assembly of master regulators and transcriptional co-regulators at developmental stage-specific enhancers controls gene expression programs and temporal regulation of transcriptional networks in a mammalian genome. Examination of various histone modifications and transcription factor occupancy by ChIP-seq in fetal and adult proerythroblasts.
2012-10-05 | E-GEOD-36985 | biostudies-arrayexpress
Project description:Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes
| PRJNA434651 | ENA
Project description:We report the comparative investigation of genome-wide chromatin state maps, transcription factor (TF) occupancy, and gene expression profiles from developing red cell precursors at two developmental stages. Contrasting the similarities and differences between fetal and adult erythropoiesis provides important insights into the erythroid gene expression programs and gene regulatory networks. Specifically, comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that master regulators, such as GATA1 and TAL1, cooperatively act within active enhancers but have little predictive value for stage-specific enhancer activity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of adult-stage expression program. Thus, the combinatorial assembly of master regulators and transcriptional co-regulators at developmental stage-specific enhancers controls gene expression programs and temporal regulation of transcriptional networks in a mammalian genome.
2012-10-05 | GSE36985 | GEO
Project description:Erythropoiesis occurs first in the yolk sac as a transit “primitive” form, then is gradually re-placed by the “definitive” form in the fetal liver (FL) during fetal development and in the bone marrow (BM) postnatal. While it is well known that differences exist between primitive and de-finitive erythropoiesis, the similarities and differences between FL and BM definitive erythropoi-esis have not been studied. Here we performed comprehensive comparisons of erythroid progen-itors and precursors at all maturational stages sorted from E16.5 FL and adult BM. Transcriptome comparison revealed that genes with increased expression in FL BFU-E were en-riched in cell division. Interestingly, the expression levels of glucocorticoid receptor Nr3c1, Myc and Myc downstream target Ccna2, were significantly higher in FL BFU-E, indicating the role of Nr3c1-Myc-Ccna2 axis in the enhanced proliferation/cell division of FL BFU-E cells. At the CFU-E stage, the expression of genes associated with hemoglobin biosynthesis were much higher in FL CFU-E, indicating more hemoglobin production. During terminal erythropoiesis, overall temporal patterns in gene expression were conserved between FL and BM. While biological pro-cesses related to translation, TCA and hypoxia response were upregulated in FL erythroblasts, that related to antiviral signal pathway were upregulated in BM erythroblasts. Our findings un-covered previously unrecognized differences between FL and BM definitive erythropoiesis and provide novel insights into erythropoiesis.
2024-06-11 | GSE269127 | GEO