Frontotemporal dementia (FTD) describes a group of clinically heterogeneous conditions that frequently affect people under the age of 65 (Le Ber et al., 2013). There are multiple genetic causes of FTD, including coding or splice-site mutations in MAPT, GRN mutations that lead to haploinsufficiency of progranulin protein, and a hexanucleotide GGGGCC repeat expansion in C9ORF72. Pathologically, FTD is characterised by abnormal protein accumulations in neurons and glia. These aggregates can be composed of the microtubule-associated protein tau (observed in FTD with MAPT mutations), the DNA/RNA-binding protein TDP-43 (seen in FTD with mutations in GRN or C9ORF72 repeat expansions) or dipeptide proteins generated by repeat associated non-ATG translation of the C9ORF72 repeat expansion. There are currently no disease-modifying therapies for FTD and the availability of in vitro models that recapitulate pathologies in a disease-relevant cell type would accelerate the development of novel therapeutics. It is now possible to generate patient-specific stem cells through the reprogramming of somatic cells from a patient with a genotype/phenotype of interest into induced pluripotent stem cells (iPSCs). iPSCs can subsequently be differentiated into a plethora of cell types including neurons, astrocytes and microglia. Using this approach has allowed researchers to generate in vitro models of genetic FTD in human cell types that are largely inaccessible during life. In this review we explore the recent progress in the use of iPSCs to model FTD, and consider the merits, limitations and future prospects of this approach.

额颞叶痴呆 (FTD) 描述了一组经常影响 65 岁以下人群的临床异质性疾病（Le Ber 等，2013）。有FTD的多种遗传原因，包括在编码或剪接位点突变MAPT，GRN突变导致颗粒体蛋白的单倍剂量不足，和在一个六核苷酸GGGGCC重复扩增C9ORF72。在病理学上，FTD 的特征是神经元和神经胶质中的异常蛋白质积累。这些聚集体可以由微管相关蛋白 tau（在具有MAPT突变的FTD 中观察到）、DNA/RNA 结合蛋白 TDP-43（在具有GRN或C9ORF72突变的 FTD 中观察到）组成重复扩增）或由C9ORF72 的重复相关非 ATG 翻译产生的二肽蛋白重复扩展。目前没有针对 FTD 的疾病修饰疗法，并且在与疾病相关的细胞类型中重现病理的体外模型的可用性将加速新疗法的开发。现在可以通过将具有感兴趣基因型/表型的患者的体细胞重编程为诱导多能干细胞 (iPSC) 来生成患者特异性干细胞。iPSC 随后可以分化为多种细胞类型，包括神经元、星形胶质细胞和小胶质细胞。使用这种方法，研究人员可以在人类细胞类型中生成遗传 FTD 的体外模型，这些细胞类型在生命中基本上无法获得。在这篇综述中，我们探讨了使用 iPSC 模拟 FTD 的最新进展，并考虑了这种方法的优点、局限性和未来前景。