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用于研究中枢神经系统疾病中神经胶质线索的干细胞工程方法。

Stem cell engineering approaches for investigating glial cues in central nervous system disorders.

机构信息

Department of Bioengineering, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

Department of Bioengineering, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

出版信息

Curr Opin Biotechnol. 2024 Jun;87:103131. doi: 10.1016/j.copbio.2024.103131. Epub 2024 Apr 9.

DOI:10.1016/j.copbio.2024.103131
PMID:38599012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11351366/
Abstract

Glial cells are important in maintaining homeostasis for neurons in the central nervous system (CNS). During CNS disease or after injury, glia react to altered microenvironments and often acquire altered functions that contribute to disease pathology. A major focus for research is utilizing stem cell (SC)-derived glia as a potential renewable source for cell replacement to restore function, including neuronal support, and as a model for disease states to identify therapeutic targets. In this review, we focus on SC differentiation protocols for deriving three types of glial cells, astrocytes, oligodendrocytes, and microglia. These SC-derived glia can be used to identify critical cues that contribute to CNS disease progression and aid in investigation of therapeutic targets.

摘要

胶质细胞在维持中枢神经系统(CNS)神经元的内环境稳定方面起着重要作用。在 CNS 疾病或损伤后,胶质细胞会对改变的微环境做出反应,通常会获得改变的功能,从而导致疾病的病理变化。研究的一个主要重点是利用干细胞(SC)衍生的胶质细胞作为一种潜在的可再生细胞替代物来源,以恢复功能,包括神经元支持,并作为疾病状态的模型,以确定治疗靶点。在这篇综述中,我们重点介绍了用于分化三种类型的胶质细胞(星形胶质细胞、少突胶质细胞和小胶质细胞)的 SC 分化方案。这些 SC 衍生的胶质细胞可用于鉴定导致 CNS 疾病进展的关键线索,并有助于研究治疗靶点。

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Stem cell engineering approaches for investigating glial cues in central nervous system disorders.用于研究中枢神经系统疾病中神经胶质线索的干细胞工程方法。
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本文引用的文献

1
C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9.C9orf72-ALS 人类诱导多能干细胞小胶质细胞通过 MMP9 对共培养的运动神经元产生炎症反应和毒性。
Nat Commun. 2023 Sep 22;14(1):5898. doi: 10.1038/s41467-023-41603-0.
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Role of Astrocytes in Parkinson's Disease Associated with Genetic Mutations and Neurotoxicants.星形胶质细胞在与基因突变和神经毒素相关的帕金森病中的作用。
Cells. 2023 Feb 15;12(4):622. doi: 10.3390/cells12040622.
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Oligodendrogenesis and myelination tracing in a CRISPR/Cas9-engineered brain microphysiological system.
CRISPR/Cas9 工程化脑微生理系统中的少突胶质细胞生成和髓鞘形成追踪
Front Cell Neurosci. 2023 Jan 19;16:1094291. doi: 10.3389/fncel.2022.1094291. eCollection 2022.
4
FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms.FUS-ALS 诱导多能干细胞衍生的星形胶质细胞通过毒性获得和支持丧失机制损害人类运动单位。
Mol Neurodegener. 2023 Jan 18;18(1):5. doi: 10.1186/s13024-022-00591-3.
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Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function.细胞内淀粉样β沉淀影响人诱导多能干细胞源性星形胶质细胞支持神经元功能的能力。
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Cardiolipin released by microglia can act on neighboring glial cells to facilitate the uptake of amyloid-β (1-42).小胶质细胞释放的心磷脂可作用于邻近的神经胶质细胞,以促进β淀粉样蛋白(1-42)的摄取。
Mol Cell Neurosci. 2023 Mar;124:103804. doi: 10.1016/j.mcn.2022.103804. Epub 2022 Dec 30.
7
Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes.小分子筛选揭示了调控干细胞来源星形胶质细胞中 C4 分泌的途径。
Stem Cell Reports. 2023 Jan 10;18(1):237-253. doi: 10.1016/j.stemcr.2022.11.018. Epub 2022 Dec 22.
8
An altered extracellular matrix-integrin interface contributes to Huntington's disease-associated CNS dysfunction in glial and vascular cells.异常的细胞外基质-整合素界面导致亨廷顿病相关的神经胶质细胞和血管细胞的中枢神经系统功能障碍。
Hum Mol Genet. 2023 Apr 20;32(9):1483-1496. doi: 10.1093/hmg/ddac303.
9
The efficient generation of knockout microglia cells using a dual-sgRNA strategy by CRISPR/Cas9.利用CRISPR/Cas9的双sgRNA策略高效生成小胶质细胞敲除细胞。
Front Mol Neurosci. 2022 Oct 13;15:1008827. doi: 10.3389/fnmol.2022.1008827. eCollection 2022.
10
Deterministic programming of human pluripotent stem cells into microglia facilitates studying their role in health and disease.将人类多能干细胞确定性编程为小神经胶质细胞有助于研究它们在健康和疾病中的作用。
Proc Natl Acad Sci U S A. 2022 Oct 25;119(43):e2123476119. doi: 10.1073/pnas.2123476119. Epub 2022 Oct 17.