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大规模分化 iPSC 来源的肌萎缩侧索硬化症和对照受试者的运动神经元。

Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects.

机构信息

The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.

出版信息

Neuron. 2023 Apr 19;111(8):1191-1204.e5. doi: 10.1016/j.neuron.2023.01.010. Epub 2023 Feb 9.

Abstract

Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack of well-curated lines from a large array of participants. Answer ALS has generated over 1,000 iPSC lines from control and amyotrophic lateral sclerosis (ALS) patients along with clinical and whole-genome sequencing data. The current report summarizes cell marker and gene expression in motor neuron cultures derived from 92 healthy control and 341 ALS participants using a 32-day differentiation protocol. This is the largest set of iPSCs to be differentiated into motor neurons, and characterization suggests that cell composition and sex are significant sources of variability that need to be carefully controlled for in future studies. These data are reported as a resource for the scientific community that will utilize Answer ALS data for disease modeling using a wider array of omics being made available for these samples.

摘要

利用诱导多能干细胞(iPSC)来理解神经疾病的机制具有很大的潜力;然而,缺乏来自大量参与者的精心培育的细胞系。Answer ALS 已经从对照组和肌萎缩侧索硬化症(ALS)患者中生成了超过 1000 个 iPSC 系,以及临床和全基因组测序数据。本报告总结了使用 32 天分化方案从 92 名健康对照组和 341 名 ALS 参与者中获得的运动神经元培养物中的细胞标志物和基因表达。这是最大的一组分化为运动神经元的 iPSC,其特征表明细胞组成和性别是变异性的重要来源,在未来的研究中需要仔细控制。这些数据被作为一个资源报告给科学界,该科学界将利用 Answer ALS 数据对疾病进行建模,同时提供这些样本的更广泛的组学数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ec/10557526/1345a9ff18bd/nihms-1930043-f0002.jpg

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