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

BMC Genomics

Haibo Jia¹  Weiping Yuan³  Xiangdong Fang⁴  Tao Cheng³  Anskar Yu-Hung Leung²  Xiaofan Zhu³  Xiaomin Wang³  Qiong Jia¹  Yang Wan³  Zhaojun Zhang⁴  Qian Zhang⁴  Binfeng Song¹ 

[1] Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China;Department of Medicine, University of Hong Kong, QMH 418, Hong Kong, China;State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China

关键词: RPS24;    RNA-seq;    miRNA-seq;    hematopoiesis;    DBA;   

Others  :  1140920
DOI  :  10.1186/1471-2164-15-759

 received in 2014-03-27, accepted in 2014-08-29,  发布年份 2014

【 摘 要 】

Background

Diamond–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.

Results

In 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.

Conclusions

The 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.

【 授权许可】

   
2014 Song et al.; licensee BioMed Central Ltd.

【 图 表 】

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