患者特异性iPS细胞（诱导多能干细胞）被看作是模拟遗传疾病和开发治疗它们的新方法的关键。
现在，iPS 细胞系已通过核重新编程从“LEOPARD”综合症（一种罕见的发育病，其特点是皮肤病灶、心脏异常和失聪）患者生成。从所生成的LEOPARD iPS细胞获得的心肌细胞有肥大特性，与这种疾病的典型特征相似——90%患有这种综合症的儿童有心脏肥大症。重新编程的细胞在各种不同的信号传导通道的构成部分中有广泛改动，其中包括RAS–MAPK，以前曾有人描述它与心脏肥大有关。利用这些细胞系，再加上可靠的分异规则，就有可能识别那些逆转病态细胞表现型的化合物。
本期封面图片所示为来自一个“LEOPARD”综合症iPS细胞的一个心肌细胞，背景上的iPS细胞群被染了色，以显示它们的DNA。(生物谷Bioon.com)
生物谷推荐原文出处：
Nature doi:10.1038/nature09005
Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome
Xonia Carvajal-Vergara,Ana Sevilla,Sunita L. D’Souza,Yen-Sin Ang,Christoph Schaniel,Dung-Fang Lee,Lei Yang,Aaron D. Kaplan,Eric D. Adler,Roye Rozov,YongChao Ge,Ninette Cohen,Lisa J. Edelmann,Betty Chang,Avinash Waghray,Jie Su,Sherly Pardo,Klaske D. Lichtenbelt,Marco Tartaglia,Bruce D. Gelb& Ihor R. Lemischka
The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS–mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems1, 2. The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.
