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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-09-04

AUTHORS

Binfeng Song, Qian Zhang, Zhaojun Zhang, Yang Wan, Qiong Jia, Xiaomin Wang, Xiaofan Zhu, Anskar Yu-Hung Leung, Tao Cheng, Xiangdong Fang, Weiping Yuan, Haibo Jia

ABSTRACT

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. More... »

PAGES

759

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2164-15-759

DOI

http://dx.doi.org/10.1186/1471-2164-15-759

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039682565

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25189322


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36 schema: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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42 schema:keywords ConclusionsThe present analysis
43 DBA
44 DBA models
45 DBA phenotype
46 Diamond-Blackfan anemia
47 HSCs
48 RNA-seq
49 RPS24
50 ResultsIn
51 analysis
52 anemia
53 apoptosis
54 biogenesis
55 cells
56 central node genes
57 class
58 clinical phenotype
59 comprehensive regulatory network
60 data analysis
61 decrease
62 defects
63 deficiency
64 deformity
65 development
66 disease
67 erythrocyte progenitor cells
68 expression
69 functional prediction
70 gene pathways
71 genes
72 genetic mutations
73 global regulatory network
74 hematopoiesis
75 hematopoiesis process
76 hematopoietic defects
77 human diseases
78 important miRNAs
79 insights
80 key miRNAs
81 mechanism
82 miR-142-3p
83 miRNA
84 miRNAs
85 model
86 morpholino
87 mutations
88 network
89 node genes
90 p53 pathway
91 pathogenesis
92 pathway
93 phenotype
94 physical deformities
95 prediction
96 present analysis
97 primitive hematopoiesis
98 process
99 progenitor cells
100 protein
101 regulatory networks
102 ribosome biogenesis
103 ribosome proteins
104 seq data analysis
105 significant decrease
106 study
107 systematic transcriptome analysis
108 transcriptome analysis
109 vascular development
110 zebrafish
111 zebrafish model
112 schema:name Systematic transcriptome analysis of the zebrafish model of diamond-blackfan anemia induced by RPS24 deficiency
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