iPSC toolbox for understanding and repairing disrupted brain circuits in autism.
iPSC toolbox for understanding and repairing disrupted brain circuits in autism.
复制标题
IPSC工具箱，用于理解和修复自闭症中脑电路的破坏。
DOI：
10.1038/s41380-021-01288-7
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发表时间：
2022-01
影响因子：
11
通讯作者：
Shcheglovitov A
中科院分区：
文献类型：
--
作者：
Chiola S;Edgar NU;Shcheglovitov A
在过去的十年里，在将自闭症谱系障碍(ASD)定义为大脑连接障碍方面取得了巨大的进展。事实上，全脑成像研究揭示了自闭症患者大脑连接的改变，遗传学研究发现了调节突触发育和功能的基因中罕见的自闭症相关突变。然而，目前还不清楚特定的突变如何改变不同脑区神经元连接的发展，以及改变的连接是否可以通过治疗恢复。主要的挑战是缺乏临床前模型来概括人类发展的重要方面，以研究连通性。通过最近的技术创新，现在有可能从诱导的多能干细胞(IPSCs)中产生患者或突变特异性的人类神经元或器官，并在体外或体内研究异种移植到完整的啮齿动物脑中后连接的变化。在这里，我们讨论神经发育过程中的缺陷如何导致大脑连接异常，以及如何使用基于IPSC的模型来识别异常连接，并深入了解潜在的细胞和分子机制，以开发新的治疗方法。
Over the past decade, tremendous progress has been made in defining autism spectrum disorder (ASD) as a disorder of brain connectivity. Indeed, whole-brain imaging studies revealed altered connectivity in the brains of individuals with ASD, and genetic studies identified rare ASD-associated mutations in genes that regulate synaptic development and function. However, it remains unclear how specific mutations alter the development of neuronal connections in different brain regions and whether altered connections can be restored therapeutically. The main challenge is the lack of preclinical models that recapitulate important aspects of human development for studying connectivity. Through recent technological innovations, it is now possible to generate patient- or mutation-specific human neurons or organoids from induced pluripotent stem cells (iPSCs) and to study altered connectivity in vitro or in vivo upon xenotransplantation into an intact rodent brain. Here, we discuss how deficits in neurodevelopmental processes may lead to abnormal brain connectivity and how iPSC-based models can be used to identify abnormal connections and to gain insights into underlying cellular and molecular mechanisms to develop novel therapeutics.
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影响因子：
64.5
作者：
Andersen J;Revah O;Miura Y;Thom N;Amin ND;Kelley KW;Singh M;Chen X;Thete MV;Walczak EM;Vogel H;Fan HC;Paşca SP
通讯作者：
Paşca SP
影响因子：
7.6
作者：
Chang, Andrew D.;Berges, Victoria A.;Reti, Irving M.
通讯作者：
Reti, Irving M.
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：
5.3
作者：
Belmonte, MK;Allen, G;Webb, SJ
通讯作者：
Webb, SJ
影响因子：
16.2
作者：
Alcamo, Elizabeth A.;Chirivella, Laura;McConnell, Susan K.
通讯作者：
McConnell, Susan K.