Unknown,Transcriptomics,Genomics,Proteomics

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Assessment of hematopoietic failure due to RPL11 deficiency in a zebrafish model of DiamondM-bM-^@M-^SBlackfan anemia by deep sequencing

ABSTRACT: To comprehensively reflect the impact of RPL11 deficiency on the transcriptome of zebrafish embryos, we collected 40M-bM-^@M-^S50 RPL11-deficient and MO control zebrafish embryos at 48 hpf from separate experiments and constructed two mRNA-seq sequencing libraries in parallel. High-throughput sequencing was performed on the Hi-Seq2000 sequencing platform in parallel. The number of sequenced gene transcript reads was 35M-bM-^@M-^S40 million. 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 c-myb and HSC transcription factor tal1 and hoxb4a in RPL11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC differentiation and proliferation. However, RPL11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes. Compare 2 different transcriptomes of RPL11-deficient and MO control zebrafish embryos

ORGANISM(S): Danio rerio

SUBMITTER: yadong yang

PROVIDER: E-GEOD-51326 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Zhang Zhaojun Z Jia Haibo H Zhang Qian Q Wan Yang Y Zhou Yang Y Jia Qiong Q Zhang Wanguang W Yuan Weiping W Cheng Tao T Zhu Xiaofan X Fang Xiangdong X

BMC genomics 20131217

<h4>Background</h4>Diamond-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 under ...[more]

PMID: 24341334

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Project description:The aryl hydrocarbon receptor repressor (AHRR) is a bHLH-PAS protein closely related to the aryl hydrocarbon receptor (AHR). AHRR is a transcriptional repressor of AHR and hypoxia-inducible factor (HIF) and is regulated by an AHR-dependent mechanism. Zebrafish possess two AHRR paralogs; AHRRa regulates constitutive AHR signaling during development, while AHRRb regulates polyaromatic hydrocarbon-induced gene expression. However, very little is known about the endogenous roles of AHRRs in development and physiology. The objective of this study was to elucidate the role of AHRRs during zebrafish development using a loss-of-function approach followed by microarray analysis. Zebrafish embryos were microinjected with morpholino oligonucleotides (MO) against AHRRa or AHRRb to disrupt endogenous signaling during development. At 72 hours post-fertilization (hpf), embryos were sampled for microarray analysis. Agilent microarray analysis revealed altered expression of 279 and 116 genes with knockdown of AHRRa and AHRRb, respectively. In AHRRa-morphant embryos, 97 genes were up-regulated and 182 genes were down-regulated. Among the differentially expressed genes were a large number related to photoreceptor development, including cone-specific genes such as short-wave, medium-wave and long-wave sensitive opsins (opn1sw1, opn1sw2, opn1mw1, opn1lw2), phosphodiesterases (pde6H, pde6C), retinol binding protein (rbp4l), phosducin, and arrestin. These results suggest that AHRRa may be involved in photoreceptor development. In addition, AHRRa knockdown also caused up-regulation of embryonic hemoglobin (hbbe3), suggesting a role for AHRR in regulating hematopoiesis. Knockdown of AHRRb caused up-regulation of 31 genes and down-regulation of 85 genes, without enrichment of genes related to any specific biological process. Overall, these results suggest that AHRRs play multiple roles during development. Three different treatment conditions (Control-MO, AHRRa-MO and AHRRb-MO) and two replicates per treatment

Dataset Information

Assessment of hematopoietic failure due to RPL11 deficiency in a zebrafish model of DiamondM-bM-^@M-^SBlackfan anemia by deep sequencing

Publications

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

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