Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders.
Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders.
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DOI：
10.1007/s40473-016-0100-7
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发表时间：
2016-12
影响因子：
1.7
通讯作者：
Christian KM
中科院分区：
文献类型：
--
作者：
Temme SJ;Maher BJ;Christian KM
诱导多能干细胞（iPSC）可以从人类患者组织样本中产生，分化成任何体细胞类型，并在受控培养条件下进行研究。我们回顾了如何使用iPSCs来研究精神疾病的遗传因素和生物学机制，以及在研究中综合数据的考虑。来自患者特异性iPSC研究的结果通常揭示与死后和脑成像研究一致的细胞表型。不可预测的发现说明了iPSC作为发现工具的力量，但也可能归因于建模动态神经网络的局限性或识别受影响最严重的神经亚型或发育阶段的困难。分化方案和类器官生成的技术进步将增强我们使用iPSC模拟精神疾病的显著病理学的能力。该领域还将受益于对iPSC研究的背景驱动解释，这些研究认识到所有潜在的变异性来源，包括患者病理学、遗传风险因素和受影响细胞亚型的差异。
Induced pluripotent stem cells (iPSCs) can be generated from human patient tissue samples, differentiated into any somatic cell type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies. Results from patient specific-iPSC studies often reveal cellular phenotypes consistent with postmortem and brain imaging studies. Unpredicted findings illustrate the power of iPSCs as a discovery tool, but may also be attributable to limitations in modeling dynamic neural networks or difficulty in identifying the most affected neural subtype or developmental stage. Technological advances in differentiation protocols and organoid generation will enhance our ability to model the salient pathology underlying psychiatric disorders using iPSCs. The field will also benefit from context-driven interpretations of iPSC studies that recognize all potential sources of variability, including differences in patient symptomatology, genetic risk factors and affected cellular subtype.