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Transcriptome analysis of Rpl11-deficient zebrafish model of Diamond-Blackfan Anemia.

ABSTRACT: To comprehensively reflect the roles of Rpl11 on the transcriptome of zebrafish model of Diamond-Blackfan Anemia (DBA), we performed whole-genome transcriptome sequencing on the Illumina Hi-Seq 2000 sequencing platform. Two different transcriptomes of zebrafish Rpl11-deficient and control Morpholino (Mo) embryos were collected and analyzed. The experimental design and methods, including sample preparation, RNA-Seq data evaluation and treatment, were described in details so that representative high-throughput sequencing data were acquired for assessing the actual impacts of Rpl11 on zebrafish embryos. We provided the accession number GSE51326 for easy access to the database.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC4535996 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Transcriptome analysis of Rpl11-deficient zebrafish model of Diamond-Blackfan Anemia.

Zhang Zhaojun Z Jia Haibo H Zhang Qian Q Wan Yang Y Song Binfeng B Jia Qiong Q Liu Hanzhi H Zhu Xiaofan X Fang Xiangdong X

Genomics data 20140617

To comprehensively reflect the roles of Rpl11 on the transcriptome of zebrafish model of Diamond-Blackfan Anemia (DBA), we performed whole-genome transcriptome sequencing on the Illumina Hi-Seq 2000 sequencing platform. Two different transcriptomes of zebrafish Rpl11-deficient and control Morpholino (Mo) embryos were collected and analyzed. The experimental design and methods, including sample preparation, RNA-Seq data evaluation and treatment, were described in details so that representative hi ...[more]

PMID: 26484089

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Systematic transcriptome analysis of the zebrafish model of diamond-blackfan anemia induced by RPS24 deficiency.

Project description:BackgroundDiamond-Blackfan anemia (DBA) is a class of human diseases linked to defective ribosome biogenesis that results in clinical phenotypes. Genetic mutations in ribosome protein (RP) genes lead to DBA phenotypes, including hematopoietic defects and physical deformities. However, little is known about the global regulatory network as well as key miRNAs and gene pathways in the zebrafish model of DBA.ResultsIn this study, we establish the DBA model in zebrafish using an RPS24 morpholino and found that RPS24 is required for both primitive hematopoiesis and definitive hematopoiesis processes that are partially mediated by the p53 pathway. Several deregulated genes and miRNAs were found to be related to hematopoiesis, vascular development and apoptosis in RPS24-deficient zebrafish via RNA-seq and miRNA-seq data analysis, and a comprehensive regulatory network was first constructed to identify the mechanisms of key miRNAs and gene pathways in the model. Interestingly, we found that the central node genes in the network were almost all targeted by significantly deregulated miRNAs. Furthermore, the enforced expression of miR-142-3p, a uniquely expressed miRNA, causes a significant decrease in primitive erythrocyte progenitor cells and HSCs.ConclusionsThe present analyses demonstrate that the comprehensive regulatory network we constructed is useful for the functional prediction of new and important miRNAs in DBA and will provide insights into the pathogenesis of mutant rps24-mediated human DBA disease.

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Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing.

Project description:BackgroundDiamond-Blackfan anemia is a rare congenital red blood cell dysplasia that develops soon after birth. RPL11 mutations account for approximately 4.8% of human DBA cases with defective hematopoietic phenotypes. However, the mechanisms by which RPL11 regulates hematopoiesis in DBA remain elusive. In this study, we analyzed the transcriptome using deep sequencing data from an Rpl11-deficient zebrafish model to identify Rpl11-mediated hematopoietic failure and investigate the underlying mechanisms.ResultsWe characterized hematological defects in Rpl11-deficient zebrafish embryos by identifying affected hematological genes, hematopoiesis-associated pathways, and regulatory networks. We found that hemoglobin biosynthetic and hematological defects in Rpl11-deficient zebrafish were related to dysregulation of iron metabolism-related genes, including tfa, tfr1b, alas2 and slc25a37, which are involved in heme and hemoglobin biosynthesis. In addition, we found reduced expression of the hematopoietic stem cells (HSC) marker cmyb and HSC transcription factors tal1 and hoxb4a in Rpl11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC formation, differentiation, and proliferation. However, Rpl11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes.ConclusionWe identified hematopoietic failure of Rpl11-deficient zebrafish embryos using transcriptome deep sequencing and elucidated potential underlying mechanisms. The present analyses demonstrate that Rpl11-deficient zebrafish may serve as a model of DBA and may provide insights into the pathogenesis of mutant RPL11-mediated human DBA disease.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations.

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Systematic Transcriptome Analysis of Zebrafish Model of Diamond-Blackfan Anemia from RPS24 Deficiency

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-05-18 | E-GEOD-54270 | biostudies-arrayexpress

Assessment of hematopoietic failure due to RPL11 deficiency in a zebrafish model of Diamond–Blackfan anemia by deep sequencing

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Diamond-Blackfan anemia.

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Diamond-Blackfan anemia.

Project description:Diamond-Blackfan anemia (DBA) was the first ribosomopathy described and is a constitutional inherited bone marrow failure syndrome. Erythroblastopenia is the major characteristic of the disease, which is a model for ribosomal diseases, related to a heterozygous allelic variation in 1 of the 20 ribosomal protein genes of either the small or large ribosomal subunit. The salient feature of classical DBA is a defect in ribosomal RNA maturation that generates nucleolar stress, leading to stabilization of p53 and activation of its targets, resulting in cell-cycle arrest and apoptosis. Although activation of p53 may not explain all aspects of DBA erythroid tropism, involvement of GATA1/HSP70 and globin/heme imbalance, with an excess of the toxic free heme leading to reactive oxygen species production, account for defective erythropoiesis in DBA. Despite significant progress in defining the molecular basis of DBA and increased understanding of the mechanistic basis for DBA pathophysiology, progress in developing new therapeutic options has been limited. However, recent advances in gene therapy, better outcomes with stem cell transplantation, and discoveries of putative new drugs through systematic drug screening using large chemical libraries provide hope for improvement.

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