Nan Wang , Corinne LaVasseur , Rao Riaz , Julien Papoin , Lionel Blanc , Anupama Narla
{"title":"靶向Calbindin 1可恢复人类钻石黑扇贫血模型中的红细胞功能","authors":"Nan Wang , Corinne LaVasseur , Rao Riaz , Julien Papoin , Lionel Blanc , Anupama Narla","doi":"10.1016/j.bcmd.2023.102759","DOIUrl":null,"url":null,"abstract":"<div><p><span>Diamond Blackfan anemia<span><span> (DBA) is an inherited bone marrow failure syndrome<span> characterized by congenital anomalies<span>, 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 </span></span></span>haploinsufficiency<span> of a ribosomal protein (RP) gene, with </span></span></span><em>RPS19</em><span><span><span> 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 </span>CRISPR screen in a </span>cellular model<span> of DBA and identified Calbindin 1<span> (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 </span></span></span><em>RPS19</em> 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.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330851/pdf/","citationCount":"1","resultStr":"{\"title\":\"Targeting of Calbindin 1 rescues erythropoiesis in a human model of Diamond Blackfan anemia\",\"authors\":\"Nan Wang , Corinne LaVasseur , Rao Riaz , Julien Papoin , Lionel Blanc , Anupama Narla\",\"doi\":\"10.1016/j.bcmd.2023.102759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Diamond Blackfan anemia<span><span> (DBA) is an inherited bone marrow failure syndrome<span> characterized by congenital anomalies<span>, 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 </span></span></span>haploinsufficiency<span> of a ribosomal protein (RP) gene, with </span></span></span><em>RPS19</em><span><span><span> 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 </span>CRISPR screen in a </span>cellular model<span> of DBA and identified Calbindin 1<span> (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 </span></span></span><em>RPS19</em> 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.</p></div>\",\"PeriodicalId\":8972,\"journal\":{\"name\":\"Blood Cells Molecules and Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330851/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Blood Cells Molecules and Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1079979623000360\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Cells Molecules and Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1079979623000360","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.
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.