ĭBA is a rare congenital red blood cell dysplasia that develops soon after birth. It was also observed that Rpl22l1 plays essential roles in hematopoiesis, but acts independently of p53 and does not induce apoptosis. Interestingly, these hematopoietic defects were rescued by increased RP expression or reduced p53 activity in zebrafish and in erythroid progenitor cells from DBA patients. Because erythroid progenitor cells are highly sensitive to p53 activation, subsequent activation of the p53 pathway in erythroid progenitor cells leads to cell cycle arrest and apoptosis and finally to hematopoietic disorders. ![]() ![]() Defective ribosome biosynthesis leads to excessive release of RPs such as RPL5 and RPL11, which may increase p53 activity by activating the RPS MDM2-p53 signaling pathway. Mutations in RP genes reduce the efficiency of ribosome biogenesis, which is indispensable for immature erythrocytes in early and rapid growth phases. Although RP dysfunction affects multiple tissues and systems, pathological defects in hematopoietic systems, such as aberrant development in Diamond–Blackfan anemia (DBA), are the most frequently observed phenotypes. Ribosomal protein dysfunction causes abnormal ribosomal particle assembly and affects protein synthesis in all cell types. The present analyses demonstrate that Rpl11-deficient zebrafish may serve as a model of DBA and may provide insights into the pathogenesis of mutant RPL11-mediated human DBA disease. We identified hematopoietic failure of Rpl11-deficient zebrafish embryos using transcriptome deep sequencing and elucidated potential underlying mechanisms. However, Rpl11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes. In addition, we found reduced expression of the hematopoietic stem cells (HSC) marker cmyb and HSC transcription factors tal1 and hoxb4a in Rpl11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC formation, differentiation, and proliferation. We found that hemoglobin biosynthetic and hematological defects in Rpl11-deficient zebrafish were related to dysregulation of iron metabolism-related genes, including tfa, tfr1b, alas2 and slc25a37, which are involved in heme and hemoglobin biosynthesis. ![]() We characterized hematological defects in Rpl11-deficient zebrafish embryos by identifying affected hematological genes, hematopoiesis-associated pathways, and regulatory networks. In this study, we analyzed the transcriptome using deep sequencing data from an Rpl11-deficient zebrafish model to identify Rpl11-mediated hematopoietic failure and investigate the underlying mechanisms. However, the mechanisms by which RPL11 regulates hematopoiesis in DBA remain elusive. RPL11 mutations account for approximately 4.8% of human DBA cases with defective hematopoietic phenotypes. Diamond–Blackfan anemia is a rare congenital red blood cell dysplasia that develops soon after birth.
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