Reaching into the toolbox: Stem cell models to study neuropsychiatric disorders.

Reaching into the toolbox: Stem cell models to study neuropsychiatric disorders.
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DOI:
10.1016/j.stemcr.2021.12.015
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发表时间:
2022-02-08
期刊:
影响因子:
5.9
通讯作者:
Marchetto MC
Marchetto MC
中科院分区:
医学1区
文献类型:
--
作者:
Whiteley JT;Fernandes S;Sharma A;Mendes APD;Racha V;Benassi SK;Marchetto MC

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遗传学、分子生物学和干细胞生物学的最新进展加速了我们对神经精神疾病的理解,如自闭症谱系障碍(ASD)、重度抑郁症(MDD)、双相情感障碍(BD)和精神分裂症(SZ)。这一进展突出了人类大脑和精神疾病从生物化学到细胞水平的难以置信的复杂性。神经精神疾病的复杂性在于其多基因性、细胞和大脑区域的互联性以及人类特异性神经发育过程的失调。在这里,我们讨论了可用的工具,包括CRISPR-Cas9,以及这些工具在开发基于细胞的二维(2D)模型和三维脑器官模型中的应用,这些模型可以更好地代表和揭示神经精神疾病病理生理学的复杂性。在这篇综述中,Marchetto及其同事讨论了现有的基因编辑工具,包括CRISPR-Cas9,以及这些工具在开发基于细胞的二维(2D)模型和神经精神疾病的三维脑器官模型中的应用。他们描述了这些方法的优点和局限性,以及未来要进行的工作,以产生更多与神经精神疾病生理相关的模型。
Recent advances in genetics, molecular biology, and stem cell biology have accelerated our understanding of neuropsychiatric disorders, like autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). This progress highlights the incredible complexity of both the human brain and mental illnesses from the biochemical to the cellular level. Contributing to the complexity of neuropsychiatric disorders are their polygenic nature, cellular and brain region interconnectivity, and dysregulation of human-specific neurodevelopmental processes. Here, we discuss available tools, including CRISPR-Cas9, and the applications of these tools to develop cell-based two-dimensional (2D) models and 3D brain organoid models that better represent and unravel the intricacies of neuropsychiatric disorder pathophysiology. In this review, Marchetto and colleagues discuss available gene-editing tools, including CRISPR-Cas9, and the applications of these tools to develop cell-based two-dimensional (2D) models and 3D brain organoid models of neuropsychiatric disorders. They describe both the strengths and limitations of such approaches, as well as future work to be conducted to generate more physiologically relevant models of neuropsychiatric disorders.
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