Current progress in understanding schizophrenia using genomics and pluripotent stem cells: A meta-analytical overview.
Current progress in understanding schizophrenia using genomics and pluripotent stem cells: A meta-analytical overview.
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DOI：
10.1016/j.schres.2022.11.001
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发表时间：
2024-11-01
影响因子：
4.5
通讯作者：
Stern, Shani
中科院分区：
文献类型：
--
作者：
Choudhary, Ashwani;Peles, David;Stern, Shani
精神分裂症（SCZ）是一种复杂的、遗传性的多基因神经精神疾病，它使患者丧失功能，并降低患者的预期寿命和生活质量。SCZ患者的常见和罕见变异体研究已经提供了在SCZ病理生理背景下具有重要意义的近100个基因组位点。来自临床样本的转录组学研究已经了解了SCZ患者的差异表达基因（DEGs）和非编码rna。尽管取得了这些进展，但没有发现SCZ的致病基因，因此很难在动物模型中概括SCZ。在过去的十年中，基于诱导多能干细胞（iPSCs）的模型通过研究患者ipsc衍生的2D神经元培养物和3D脑类器官，帮助理解SCZ的神经表型。在此，我们综合了大量关于SCZ遗传学和基于SCZ ipsc的模型的文献，对目前的进展和进展进行了简单的概述。虽然需要利用这些技术进步进一步了解SCZ的遗传学和病理生理机制，但最近的方法已经允许描述重要的细胞机制和受SCZ影响的生物学途径。
Schizophrenia (SCZ) is a complex, heritable and polygenic neuropsychiatric disease, which disables the patients as well as decreases their life expectancy and quality of life. Common and rare variants studies on SCZ subjects have provided >100 genomic loci that hold importance in the context of SCZ pathophysiology. Transcriptomic studies from clinical samples have informed about the differentially expressed genes (DEGs) and non-coding RNAs in SCZ patients. Despite these advancements, no causative genes for SCZ were found and hence SCZ is difficult to recapitulate in animal models. In the last decade, induced Pluripotent Stem Cells (iPSCs)-based models have helped in understanding the neural phenotypes of SCZ by studying patient iPSC-derived 2D neuronal cultures and 3D brain organoids. Here, we have aimed to provide a simplistic overview of the current progress and advancements after synthesizing the enormous literature on SCZ genetics and SCZ iPSC-based models. Although further understanding of SCZ genetics and pathophysiological mechanisms using these technological advancements is required, the recent approaches have allowed to delineate important cellular mechanisms and biological pathways affected in SCZ.