患者特異性iPS細(xì)胞（誘導(dǎo)多能干細(xì)胞）被看作是模擬遺傳疾病和開(kāi)發(fā)治療它們的新方法的關(guān)鍵,。
現(xiàn)在,，iPS 細(xì)胞系已通過(guò)核重新編程從“LEOPARD”綜合癥（一種罕見(jiàn)的發(fā)育病，其特點(diǎn)是皮膚病灶,、心臟異常和失聰）患者生成,。從所生成的LEOPARD iPS細(xì)胞獲得的心肌細(xì)胞有肥大特性，與這種疾病的典型特征相似——90%患有這種綜合癥的兒童有心臟肥大癥,。重新編程的細(xì)胞在各種不同的信號(hào)傳導(dǎo)通道的構(gòu)成部分中有廣泛改動(dòng),，其中包括RAS–MAPK，以前曾有人描述它與心臟肥大有關(guān)。利用這些細(xì)胞系,，再加上可靠的分異規(guī)則,，就有可能識(shí)別那些逆轉(zhuǎn)病態(tài)細(xì)胞表現(xiàn)型的化合物。
本期封面圖片所示為來(lái)自一個(gè)“LEOPARD”綜合癥iPS細(xì)胞的一個(gè)心肌細(xì)胞,，背景上的iPS細(xì)胞群被染了色,，以顯示它們的DNA。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
