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Abstract：
Introduction: Diamond Blackfan anemia (DBA) is a rare congenital disease characterized by defective maturation of the erythroid progenitors in the bone marrow, for which treatment involves steroids, chronic transfusions, or hematopoietic stem cells transplantation. Diamond Blackfan anemia is caused by defective ribosome biogenesis due to heterozygous pathogenic variants in one of 19 ribosomal protein (RP) genes. The decreased number of functional ribosomes leads to the activation of pro-apoptotic pathways and to the reduced translation of key genes for erythropoiesis. Results and discussion: Here we characterized the phenotype of RPS26-deficiency in a cell line derived from human umbilical cord blood erythroid progenitors (HUDEP-1 cells). This model recapitulates cellular hallmarks of Diamond Blackfan anemia including: imbalanced production of ribosomal RNAs, upregulation of pro-apoptotic genes and reduced viability, and shows increased levels of intracellular calcium. Evaluation of the expression of erythroid markers revealed the impairment of erythroid differentiation in RPS26-silenced cells compared to control cells. Conclusions: In conclusion, for the first time we assessed the effect of RPS26 deficiency in a human erythroid progenitor cell line and demonstrated that these cells can be used as a scalable model system to study aspects of DBA pathophysiology that have been refractory to detailed investigation because of the paucity of specific cell types affected in this disorder.
摘要：
简介：DiamondBlackfan贫血（DBA）是一种罕见的先天性疾病，其特征是骨髓中红系祖细胞的成熟缺陷，治疗涉及类固醇，慢性输血,或造血干细胞移植。DiamondBlackfan贫血是由19个核糖体蛋白（RP）基因之一的杂合致病变异导致的核糖体生物发生缺陷引起的。功能性核糖体数量的减少导致促凋亡途径的激活和红细胞生成关键基因翻译的减少。结果和讨论：在这里，我们表征了源自人脐带血红系祖细胞（HUDEP-1细胞）的细胞系中RPS26缺陷的表型。该模型概括了DiamondBlackfan贫血的细胞标志，包括：核糖体RNA的不平衡产生，促凋亡基因的上调和活力降低，并显示细胞内钙水平增加。红系标志物表达的评估揭示了与对照细胞相比，RPS26沉默的细胞中红系分化的损害。结论：总之，我们首次评估了RPS26缺乏对人类红系祖细胞的影响,并证明这些细胞可用作可扩展的模型系统来研究DBA病理生理学方面,这些方面由于缺乏特定的细胞类型而难以进行详细研究.
