Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs.
Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs.
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使用免整合患者来源的 iPSC 建模范可尼贫血发病机制和治疗方法
DOI：
10.1038/ncomms5330
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发表时间：
2014-07-07
影响因子：
16.6
通讯作者：
Belmonte, Juan Carlos Izpisua
中科院分区：
文献类型：
--
作者：
Liu, Guang-Hui;Suzuki, Keiichiro;Li, Mo;Qu, Jing;Montserrat, Nuria;Tarantino, Carolina;Gu, Ying;Yi, Fei;Xu, Xiuling;Zhang, Weiqi;Ruiz, Sergio;Plongthongkum, Nongluk;Zhang, Kun;Masuda, Shigeo;Nivet, Emmanuel;Tsunekawa, Yuji;Soligalla, Rupa Devi;Goebl, April;Aizawa, Emi;Kim, Na Young;Kim, Jessica;Dubova, Ilir;Li, Ying;Ren, Ruotong;Benner, Chris;del Sol, Antonio;Bueren, Juan;Pablo Trujillo, Juan;Surralles, Jordi;Cappelli, Enrico;Dufour, Carlo;Esteban, Concepcion Rodriguez;Belmonte, Juan Carlos Izpisua
范可尼贫血（FA）是一种以基因组不稳定、先天性异常、癌症易感性和骨髓（BM）衰竭为特征的隐性疾病。然而，部分由于目前疾病模型的局限性，FA的发病机制尚未完全了解。在这里，我们从FA患者中获得无整合诱导多能干细胞（iPSC），而没有遗传互补和FA-iPSC中的apotin situgene校正，以及产生isogenicFANCA缺陷的人胚胎干细胞（ESC）系。FA细胞表型在iPSC/ESC及其成体干/祖细胞衍生物中重现。通过使用无同基因致病突变对照以及细胞和基因组工具，我们的模型有助于发现新的疾病特征。我们通过鉴定几种改善FA-iPSCs造血分化的化合物来验证我们的模型作为药物筛选平台。这些化合物还能够拯救FA患者BM细胞的造血表型。
Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and reportin situgene correction in FA–iPSCs as well as the generation of isogenicFANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA–iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
9.8
作者：
Bogliolo, Massimo;Schuster, Beatrice;Surralles, Jordi
通讯作者：
Surralles, Jordi
影响因子：
20.3
作者：
Li, Yan;Chen, Shi;Yang, Feng-Chun
通讯作者：
Yang, Feng-Chun
影响因子：
4.8
作者：
Donahue, SL;Lundberg, R;Campbell, C
通讯作者：
Campbell, C
影响因子：
20.3
作者：
Anur, Praveen;Yates, Jane;Bagby, Grover C.
通讯作者：
Bagby, Grover C.