title: Systematic transcriptome analysis of the zebrafish model of diamond-blackfan anemia induced by RPS24 deficiency.
abstract: 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.
authors.forename: Binfeng
authors.initials: B
authors.lastname: Song
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jia
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
authors.forename: Anskar Yu-Hung
authors.initials: AY
authors.lastname: Leung
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: 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. fangxd@big.ac.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
authors.forename: Haibo
authors.initials: H
authors.lastname: Jia
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D015672:Erythroid Precursor Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D060172:Morpholinos / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53; D015027:Zebrafish / Q000235:genetics
chemical_list: D035683:MicroRNAs; D060172:Morpholinos; C489053:RPS24 protein, human; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53