Transcriptome Analysis Of The Zebrafish Model Of Diamond-Blackfan Anemia From RPS19Deficiency Via P53-Dependent And-Independent Pathways

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 RPS19is 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 RPS19morpholino (RPS19MO), RPS19and p53morpholino simultaneously (RPS19+p53MO) and control morpholino (Control). We found that genes enriched in the functions of hematological systems, nervous system development and skeletal and muscular disorders had significantly differential expression in RPS19MO embryos compared with Controls. Co-inhibition of p53partially alleviates the abnormalities of RPS19-deficient embryos. However, the hematopoietic genes, which were down-regulated significantly in RPS19MO 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 p53family members but also several other factors have important impacts on RPS19-deficient embryos. The detection of potential pathogenic genes and pathways provides us a new paradigm for research on DBA, which is a systematic and complex hereditary disease.