Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells.
Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells.
复制标题
使用患者衍生的多能干细胞的精神分裂症和躁郁症的疾病特征。
DOI：
10.1016/j.mcn.2016.01.003
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Karmacharya R
中科院分区：
文献类型：
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作者：
Watmuff B;Berkovitch SS;Huang JH;Iaconelli J;Toffel S;Karmacharya R
精神分裂症和双相情感障碍是复杂的精神疾病，给疾病生物学研究带来了独特的挑战。这些疾病没有客观的生物学表型，其特点是复杂的遗传学和基因-环境相互作用的显着作用。由于无法接触到感兴趣的组织——患者的神经元，对这些严重精神疾病背后的神经生物学的研究受到了阻碍。能够从患者成纤维细胞和外周血单核细胞生成诱导多能干细胞 (iPSC) 的重编程方法的出现，为使用 iPSC 衍生的神经元研究相关疾病生物学的新方法提供了可能性。虽然对患者 iPSC 的早期研究已经取得了有希望且有趣的线索，但我们在体外捕获这些疾病的复杂性的尝试仍然存在重大障碍。我们在此概述了迄今为止使用 iPSC 衍生的神经元细胞对精神分裂症和双相情感障碍进行的研究，并讨论了潜在的未来方向，这些方向可以导致识别稳健且有效的细胞表型，从而为有意义的临床进展奠定基础。
Schizophrenia and bipolar disorder are complex psychiatric disorders that present unique challenges in the study of disease biology. There are no objective biological phenotypes for these disorders, which are characterized by complex genetics and prominent roles for gene-environment interactions. The study of the neurobiology underlying these severe psychiatric disorders has been hindered by the lack of access to the tissue of interest – neurons from patients. The advent of reprogramming methods that enable generation of induced pluripotent stem cells (iPSCs) from patient fibroblasts and peripheral blood mononuclear cells has opened possibilities for new approaches to study relevant disease biology using iPSC-derived neurons. While early studies with patient iPSCs have led to promising and intriguing leads, significant hurdles remain in our attempts to capture the complexity of these disorders in vitro. We present here an overview of studies to date of schizophrenia and bipolar disorder using iPSC-derived neuronal cells and discuss potential future directions that can result in the identification of robust and valid cellular phenotypes that in turn can lay the groundwork for meaningful clinical advances.