Modeling Glanzmann thrombasthenia using patient specific iPSCs and restoring platelet aggregation function by CD41 overexpression
Modeling Glanzmann thrombasthenia using patient specific iPSCs and restoring platelet aggregation function by CD41 overexpression
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使用患者特异性 iPSC 建模 Glanzmann 血小板无力症并通过 CD41 过表达恢复血小板聚集功能
DOI：
10.1016/j.scr.2017.02.003
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发表时间：
2017
影响因子：
1.2
通讯作者：
Lin Ge
中科院分区：
文献类型：
--
作者：
Hu Liang;Du Lili;Zhao Yan;Li Wen;Ouyang Qi;Zhou Di;Lu Guangxiu;Lin Ge
血小板无力症（GT）是一种罕见的单基因出血性疾病，涉及无核血小板聚集缺陷。在这项研究中，我们产生了诱导多能干细胞（iPSCs）从皮肤成纤维细胞的GT患者与复杂的异质性突变的ITGA 2B基因。GT-iPSC可成功分化为血小板（GT-iPS-血小板）。GT-iPS-血小板为CD 41 −/CD 42 b +/CD 61 −，二磷酸腺苷（ADP）活化后血小板活化标志物（PAC-1）为阴性。体外血小板聚集试验表明，GT-iPS-platelets在体外血小板聚集试验中存在缺陷。此外，野生型ITGA 2B基因在GT-iPS血小板中的外源性表达恢复了CD 41表达和正常的血小板聚集。我们的研究表明，患者特异性iPSCs可能是基于干细胞的血小板疾病基因治疗的潜在靶点。
Glanzmann thrombasthenia (GT) is a rare monogenic hemorrhagic disorder involving aggregation defect of non-nuclear platelets. In this study we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of a GT patient with complex heterogeneous mutations ofITGA2Bgene. GT-iPSCs could be successfully differentiated into platelets (GT-iPS-platelets). GT-iPS-platelets were CD41 −/CD42b +/CD61 − and were platelet activation marker (PAC-1) negative after adenosine diphosphate (ADP) activation. Furthermore, GT-iPS-platelets were defective in platelet aggregation testsin vitro. Moreover, exogenous expression of the wild-typeITGA2Bgene in GT-iPS platelets restored CD41 expression and normal platelet aggregation. Our study suggested that patient-specific iPSCs could be a potential target of stem cell based gene therapy for platelet diseases.