Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets.
Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets.
复制标题
DOI：
10.1186/s13229-021-00417-x
复制
发表时间：
2021-02-08
期刊：
影响因子：
6.2
通讯作者：
Eggan KC
中科院分区：
文献类型：
--
作者：
Pintacuda G;Martín JM;Eggan KC
自闭症谱系障碍(ASD)是一组神经发育障碍，其特征是社交功能受损，表现为限制性和重复性行为。ASD是高度可遗传的，但在基因上是异质性的，常见和罕见的基因变异共同作用，使个人容易患上这种疾病。在这篇综述中，我们综述了最近开发人类诱导多能干细胞(IPSC)衍生的ASD相关表型模型的努力。我们首先解决了对可用的神经元IPSC衍生模型的相关性和有效性的担忧。然后，我们批判性地评估用于产生与ASD相关的细胞类型的各种分化和细胞培养方案的稳健性。通过探索迄今报道的ASD的IPSC模型，我们检查了与ASD潜在相关的细胞和神经元表型在多大程度上与发现的支持ASD的遗传变异有关。最后，我们概述了IPSC技术有希望的策略，通过这些策略，IPSC技术既可以增强基因研究的力量，识别ASD风险因素，又可以提名可能作为治疗干预共同点的ASD患者组中被干扰的路径。
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interactions as well as the presentation of restrictive and repetitive behaviors. ASD is highly heritable but genetically heterogenous with both common and rare genetic variants collaborating to predispose individuals to the disorder. In this review, we synthesize recent efforts to develop human induced pluripotent stem cell (iPSC)-derived models of ASD-related phenotypes. We firstly address concerns regarding the relevance and validity of available neuronal iPSC-derived models. We then critically evaluate the robustness of various differentiation and cell culture protocols used for producing cell types of relevance to ASD. By exploring iPSC models of ASD reported thus far, we examine to what extent cellular and neuronal phenotypes with potential relevance to ASD can be linked to genetic variants found to underlie it. Lastly, we outline promising strategies by which iPSC technology can both enhance the power of genetic studies to identify ASD risk factors and nominate pathways that are disrupted across groups of ASD patients that might serve as common points for therapeutic intervention.
登录
查看更多内容
影响因子：
56.9
作者：
Cheng, J;Kapranov, P;Gingeras, TR
通讯作者：
Gingeras, TR
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP
影响因子：
64.8
作者：
Abudayyeh OO;Gootenberg JS;Essletzbichler P;Han S;Joung J;Belanto JJ;Verdine V;Cox DBT;Kellner MJ;Regev A;Lander ES;Voytas DF;Ting AY;Zhang F
通讯作者：
Zhang F
影响因子：
10.6
作者：
Deep-Soboslay, Amy;Benes, Francine M.;Haroutunian, Vahram;Ellis, Justin K.;Kleinman, Joel E.;Hyde, Thomas M.
通讯作者：
Hyde, Thomas M.
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz