靶向Calbindin 1可恢复人类钻石黑扇贫血模型中的红细胞功能

IF 2.1 4区 医学 Q3 HEMATOLOGY Blood Cells Molecules and Diseases Pub Date : 2023-09-01 DOI:10.1016/j.bcmd.2023.102759
Nan Wang , Corinne LaVasseur , Rao Riaz , Julien Papoin , Lionel Blanc , Anupama Narla
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引用次数: 1

摘要

Diamond Blackfan贫血(DBA)是一种遗传性骨髓衰竭综合征,其特征是先天性异常、癌症易感性和严重的低增殖性贫血。它是第一种与核糖体功能障碍相关的疾病,并且>;70%的患者已被鉴定为核糖体蛋白(RP)基因单倍缺失,其中RPS19是最常见的突变。在表型和对治疗的反应方面,该疾病存在显著的变异性,这表明其他基因有助于该疾病的病理生理学和潜在的管理。为了探索这些问题,我们在DBA的细胞模型中进行了全基因组CRISPR筛选,并确定钙结合超家族成员钙结合蛋白1(CALB1)是DBA红细胞生成紊乱的潜在调节剂。我们使用在具有RPS19敲除的红系刺激培养基中培养的人来源的CD34+细胞作为DBA的模型来研究CALB1的作用。我们发现在这个DBA模型中敲低CALB1促进了红系成熟。我们还注意到CALB1敲低对细胞周期的影响。总之,我们的研究结果表明,CALB1是一种新的人类红细胞生成调节因子,并对使用CALB1作为DBA的新治疗靶点具有启示意义。
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Targeting of Calbindin 1 rescues erythropoiesis in a human model of Diamond Blackfan anemia

Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by congenital anomalies, cancer predisposition and a severe hypo-proliferative anemia. It was the first disease linked to ribosomal dysfunction and >70 % of patients have been identified to have a haploinsufficiency of a ribosomal protein (RP) gene, with RPS19 being the most common mutation. There is significant variability within the disease in terms of phenotype as well as response to therapy suggesting that other genes contribute to the pathophysiology and potential management of this disease. To explore these questions, we performed a genome-wide CRISPR screen in a cellular model of DBA and identified Calbindin 1 (CALB1), a member of the calcium-binding superfamily, as a potential modifier of the disordered erythropoiesis in DBA. We used human derived CD34+ cells cultured in erythroid stimulating media with knockdown of RPS19 as a model for DBA to study the effects of CALB1. We found that knockdown of CALB1 in this DBA model promoted erythroid maturation. We also noted effects of CALB1 knockdown on cell cycle. Taken together, our results reveal CALB1 is a novel regulator of human erythropoiesis and has implications for using CALB1 as a novel therapeutic target in DBA.

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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
42
审稿时长
14 days
期刊介绍: Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.
期刊最新文献
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