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人类多能干细胞的神经谱系分化:疾病建模的进展

Neural lineage differentiation of human pluripotent stem cells: Advances in disease modeling.

作者信息

Yan Yuan-Wei, Qian Eddie S, Woodard Lauren E, Bejoy Julie

机构信息

Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, United States.

Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, United States.

出版信息

World J Stem Cells. 2023 Jun 26;15(6):530-547. doi: 10.4252/wjsc.v15.i6.530.

DOI:10.4252/wjsc.v15.i6.530
PMID:37424945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10324500/
Abstract

Brain diseases affect 1 in 6 people worldwide. These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer's disease. Recent advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models, tissue culture models, and epidemiologic patient data that are commonly used to study brain disease. One innovative method by which to model human neurological disease is the directed differentiation of human pluripotent stem cells (hPSCs) to neural lineages including neurons, astrocytes, and oligodendrocytes. Three-dimensional models such as brain organoids have also been derived from hPSCs, offering more physiological relevance due to their incorporation of various cell types. As such, brain organoids can better model the pathophysiology of neural diseases observed in patients. In this review, we will emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models.

摘要

脑部疾病影响着全球六分之一的人口。这些疾病涵盖了从急性神经系统疾病(如中风)到慢性神经退行性疾病(如阿尔茨海默病)等多种类型。组织工程化脑部疾病模型的最新进展克服了许多与常用于研究脑部疾病的各种动物模型、组织培养模型和流行病学患者数据相关的不同缺点。一种模拟人类神经疾病的创新方法是将人类多能干细胞(hPSC)定向分化为神经谱系,包括神经元、星形胶质细胞和少突胶质细胞。诸如脑类器官等三维模型也已从hPSC中衍生出来,由于它们包含了多种细胞类型,因而具有更高的生理相关性。因此,脑类器官能够更好地模拟患者中观察到的神经疾病的病理生理学。在这篇综述中,我们将重点介绍基于hPSC的神经系统疾病组织培养模型的最新进展,以及它们如何被用于创建神经疾病模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/57e64be6cc52/WJSC-15-530-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/b08ea0dd6d43/WJSC-15-530-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/0de41f48ff30/WJSC-15-530-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/57e64be6cc52/WJSC-15-530-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/b08ea0dd6d43/WJSC-15-530-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/0de41f48ff30/WJSC-15-530-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb38/10324500/57e64be6cc52/WJSC-15-530-g003.jpg

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Generation of Human Ventral Midbrain Organoids Derived from Pluripotent Stem Cells.人胚中脑神经节器官原代细胞的培养。
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A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states.
评估在各种诱导剂影响下,源自神经干细胞的分化假神经元细胞中的凋亡水平。
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Patient-derived induced pluripotent stem cells with a mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential.携带突变的患者来源的诱导多能干细胞表现出细胞连接异常和异常的细胞分化潜能。
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Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies.诱导多能干细胞和类器官在推进神经病理学研究和治疗中的应用。
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CRISPRi/a 平台在人类诱导多能干细胞衍生的小神经胶质细胞中揭示了疾病状态的调控因子。
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