Systematic Transcriptome Analysis of Zebrafish Model of Diamond-Blackfan Anemia from RPS24 Deficiency
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PROVIDER: PRJNA236073 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptome profile of highly purified multipotential (P), erythroid (E), and myeloid (M) bone marrow progenitors from three RPS19 mutated Diamond-Blackfan anemia and six control human subjects. Two group comparison of sex and age matched subjects. Bone marrow progenitors, gene expression profiling, Diamond-Blackfan anemia, RPS19
2012-10-16 | E-GEOD-41599 | biostudies-arrayexpress
Project description:In this study, we found RPS24 is required for both the primitive hematopoiesis and definitive hematopoiesis process partly mediated by P53 pathway. With the RNA-seq and miRNA-seq technique, several deregulated genes and miRNAs were found to be related with hematopoiesis, vascular development and apoptosis process in RPS24-deficient zebrafish. Meanwhile, a comprehensive regulatory network was firstly constructed to indentify the mechanisms of key miRNAs and gene pathways in this Model of Diamond-Blackfan Anemia. Interestingly, we found that the central nodes genes in the network were almost all targeted by significantly deregulated miRNAs, with partial verification from previous studies, revealing that our network-based approach is promising for the identification of new and important miRNAs in DBA. The present study provided comprehensive potential pathogenic genes and miRNAs data that are associated with RPS24-deficient zebrafish embryos as a model of DBA, which should provide a valuable resource for understanding the complex molecular pathogenesis of mutant RPS24-mediated human diseases. Determine the differences of transcriptome between RPS24-deficient and MO control zebrafish embryos for understanding the complex molecular pathogenesis of mutant RPS24-mediated human diseases
2015-05-18 | E-GEOD-54152 | biostudies-arrayexpress
Project description:In this study, we found RPS24 is required for both the primitive hematopoiesis and definitive hematopoiesis process partly mediated by P53 pathway. With the RNA-seq and miRNA-seq technique, several deregulated genes and miRNAs were found to be related with hematopoiesis, vascular development and apoptosis process in RPS24-deficient zebrafish. Meanwhile, a comprehensive regulatory network was firstly constructed to indentify the mechanisms of key miRNAs and gene pathways in this Model of Diamond-Blackfan Anemia. Interestingly, we found that the central nodes genes in the network were almost all targeted by significantly deregulated miRNAs, with partial verification from previous studies, revealing that our network-based approach is promising for the identification of new and important miRNAs in DBA. The present study provided comprehensive potential pathogenic genes and miRNAs data that are associated with RPS24-deficient zebrafish embryos as a model of DBA, which should provide a valuable resource for understanding the complex molecular pathogenesis of mutant RPS24-mediated human diseases. Determine the differences of miRNome between RPS24-deficient and MO control zebrafish embryos for understanding the complex molecular pathogenesis of mutant RPS24-mediated human diseases
2015-05-18 | E-GEOD-54259 | biostudies-arrayexpress
Project description:In this study, we found RPS24 is required for both the primitive hematopoiesis and definitive hematopoiesis process partly mediated by P53 pathway. With the RNA-seq and miRNA-seq technique, several deregulated genes and miRNAs were found to be related with hematopoiesis, vascular development and apoptosis process in RPS24-deficient zebrafish. Meanwhile, a comprehensive regulatory network was firstly constructed to indentify the mechanisms of key miRNAs and gene pathways in this Model of Diamond-Blackfan Anemia. Interestingly, we found that the central nodes genes in the network were almost all targeted by significantly deregulated miRNAs, with partial verification from previous studies, revealing that our network-based approach is promising for the identification of new and important miRNAs in DBA. The present study provided comprehensive potential pathogenic genes and miRNAs data that are associated with RPS24-deficient zebrafish embryos as a model of DBA, which should provide a valuable resource for understanding the complex molecular pathogenesis of mutant RPS24-mediated human diseases.
2015-05-18 | GSE54259 | GEO
Project description:In this study, we found RPS24 is required for both the primitive hematopoiesis and definitive hematopoiesis process partly mediated by P53 pathway. With the RNA-seq and miRNA-seq technique, several deregulated genes and miRNAs were found to be related with hematopoiesis, vascular development and apoptosis process in RPS24-deficient zebrafish. Meanwhile, a comprehensive regulatory network was firstly constructed to indentify the mechanisms of key miRNAs and gene pathways in this Model of Diamond-Blackfan Anemia. Interestingly, we found that the central nodes genes in the network were almost all targeted by significantly deregulated miRNAs, with partial verification from previous studies, revealing that our network-based approach is promising for the identification of new and important miRNAs in DBA. The present study provided comprehensive potential pathogenic genes and miRNAs data that are associated with RPS24-deficient zebrafish embryos as a model of DBA, which should provide a valuable resource for understanding the complex molecular pathogenesis of mutant RPS24-mediated human diseases.
2015-05-18 | GSE54152 | GEO
Project description:Gene expression analysis from erythroid progenitors (CD34+/CD71(high)/CD45- mononuclear cells from the bone marrow) of patients with Diamond-Blackfan anemia (due to RPS19 mutations) and control individuals.
2014-02-28 | GSE41817 | GEO
Project description:We found that endogenously expressed RPS19 binds evolutionarily constrained intronic elements. By assessing overexpression of WT RPS19 and RPS19 harboring the most common Diamond-Blackfan anemia missense mutations, we confirmed that disease-relevant mutations alter RPS19 binding preferences in human cells.
2023-02-14 | GSE224998 | GEO
Project description:RPS19 mutations are the most common cause of the human disorder Diamond Blackfan Anemia. The R62W mutation was hypothesized to act in a dominant negative fashion and mice expressing RPS19R62W have many of the characteristics of Diamond Blackfan Anemia. Diamond-Blackfan Anemia (DBA), is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Mutations in the gene encoding Ribosomal Protein S19 (RPS19) have been identified in ~25% of DBA families. Most of these mutations disrupt either the translation or stability of the RPS19 protein and are predicted to cause DBA by haploinsufficiency. However, approximately ~30% of RPS19 mutations are missense mutations that do not alter the stability of the RPS19 protein and are hypothesized to act by a dominant negative mechanism. To formally test this hypothesis, we generated a transgenic mouse model expressing an RPS19 mutation in which an Arginine residue is replaced with a Tryptophan residue at codon 62 (RPS19R62W). Constitutive expression of RPS19R62W in developing mice was lethal. Conditional expression of RPS19R62W resulted in growth retardation, a mild anemia with reduced numbers of erythroid progenitors and significant inhibition of terminal erythroid maturation, similar to DBA. RNA profiling demonstrated over 700 dysregulated genes belonging to the same pathways that are disrupted in RNA profiles of DBA patient cells.
2011-06-29 | GSE22645 | GEO
Project description:Transcriptome profile of highly purified multipotential (P), erythroid (E), and myeloid (M) bone marrow progenitors from three RPS19 mutated Diamond-Blackfan anemia and six control human subjects.
2012-10-16 | GSE41599 | GEO
Project description:RPS19 mutations are the most common cause of the human disorder Diamond Blackfan Anemia. The R62W mutation was hypothesized to act in a dominant negative fashion and mice expressing RPS19R62W have many of the characteristics of Diamond Blackfan Anemia. Diamond-Blackfan Anemia (DBA), is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Mutations in the gene encoding Ribosomal Protein S19 (RPS19) have been identified in ~25% of DBA families. Most of these mutations disrupt either the translation or stability of the RPS19 protein and are predicted to cause DBA by haploinsufficiency. However, approximately ~30% of RPS19 mutations are missense mutations that do not alter the stability of the RPS19 protein and are hypothesized to act by a dominant negative mechanism. To formally test this hypothesis, we generated a transgenic mouse model expressing an RPS19 mutation in which an Arginine residue is replaced with a Tryptophan residue at codon 62 (RPS19R62W). Constitutive expression of RPS19R62W in developing mice was lethal. Conditional expression of RPS19R62W resulted in growth retardation, a mild anemia with reduced numbers of erythroid progenitors and significant inhibition of terminal erythroid maturation, similar to DBA. RNA profiling demonstrated over 700 dysregulated genes belonging to the same pathways that are disrupted in RNA profiles of DBA patient cells. The samples compared are RNA extracted from CD71 positive erythroblasts sorted from the bone marrow of wild type mice and mice expressing a mutant RPS19 (RPS19R62W) transgene
2011-06-29 | E-GEOD-22645 | biostudies-arrayexpress