title: Transcriptome analysis of the zebrafish model of Diamond-Blackfan anemia from RPS19 deficiency via p53-dependent and -independent pathways.
abstract: Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome that is characterized by pure red-cell aplasia and associated physical deformities. It has been proven that defects of ribosomal proteins can lead to this disease and that RPS19 is the most frequently mutated gene in DBA patients. Previous studies suggest that p53-dependent genes and pathways play important roles in RPS19-deficient embryos. However, whether there are other vital factors linked to DBA has not been fully clarified. In this study, we compared the whole genome RNA-Seq data of zebrafish embryos injected with RPS19 morpholino (RPS19 MO), RPS19 and p53 morpholino simultaneously (RPS19+p53 MO) and control morpholino (control). We found that genes enriched in the functions of hematological systems, nervous system development and skeletal and muscular disorders had significant differential expression in RPS19 MO embryos compared with controls. Co-inhibition of p53 partially alleviates the abnormalities for RPS19-deficient embryos. However, the hematopoietic genes, which were down-regulated significantly in RPS19 MO embryos, were not completely recovered by the co-inhibition of p53. Furthermore, we identified the genome-wide p53-dependent and -independent genes and pathways. These results indicate that not only p53 family members but also other factors have important impacts on RPS19-deficient embryos. The detection of potential pathogenic genes and pathways provides us a new paradigm for future research on DBA, which is a systematic and complex hereditary disease.
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, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jia
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Wanguang
authors.initials: W
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
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*; D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006413:Hematopoietic System / Q000196:embryology / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C040343:ribosomal protein S19