Modeling tuberous sclerosis complex with human induced pluripotent stem cells.
Modeling tuberous sclerosis complex with human induced pluripotent stem cells.
复制标题
用人类诱导多能干细胞模拟结节性硬化症。
DOI：
10.1007/s12519-022-00576-8
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Wen,Zhexing
中科院分区：
文献类型：
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作者：
Niu,Weibo;Siciliano,Benjamin;Wen,Zhexing
背景恶性硬化综合征（TSC）是一种常染色体显性遗传疾病，在美国的出生发病率为1：6000，其特征是在包括脑、肾、肺和皮肤在内的多个器官系统中生长非癌性肿瘤。重要的是，TSC还与显著的神经学表现相关，包括癫痫、TSC相关的神经精神障碍、智力残疾和自闭症谱系障碍。TSC 1或TSC 2基因突变是TSC的公认原因，其导致器官中TSC 1/TSC 2缺陷和雷帕霉素信号通路的哺乳动物靶点过度激活。动物模型已被广泛用于研究TSC 1/2基因对脑发育和功能的影响。尽管在理解动物模型中TSC潜在的分子机制方面取得了相当大的进展，但迫切需要一种人类特异性模型来研究TSC 1/2突变对人类神经发育的独特影响。数据来源文献综述和研究文章发表在PubMed索引期刊上。其捕获与其供体相同的风险等位基因并且具有分化成人体中几乎任何细胞类型的能力，为以前无法进入的生物系统如发育中的人脑的实证研究铺平了道路。本文综述了用人类iPSC模型模拟TSC的最新进展、存在的局限性以及未来研究的潜在方向。
BackgroundTuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a birth incidence of 1:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain, kidneys, lungs, and skin. Importantly, TSC is also associated with significant neurological manifestations including epilepsy, TSC-associated neuropsychiatric disorders, intellectual disabilities, and autism spectrum disorder. Mutations in theTSC1orTSC2genes are well-established causes of TSC, which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling pathway. Animal models have been widely used to study the effect ofTSC1/2genes on the development and function of the brain. Despite considerable progress in understanding the molecular mechanisms underlying TSC in animal models, a human-specific model is urgently needed to investigate the effects ofTSC1/2mutations that are unique to human neurodevelopment.Data sourcesLiterature reviews and research articles were published in PubMed-indexed journals.ResultsHuman-induced pluripotent stem cells (iPSCs), which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body, pave the way for the empirical study of previously inaccessible biological systems such as the developing human brain.ConclusionsIn this review, we present an overview of the recent progress in modeling TSC with human iPSC models, the existing limitations, and potential directions for future research.