来自人类诱导的多能干细胞的刺激神经元显示阿尔茨海默病患者与对照者的转录组差异
Ram Sagar1,2, Ioannis Azoidis1,2, Cristina Zivko1,2
1Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cells
|August 11, 2023
概括
研究人员从阿尔茨海默病患者和对照人群中产生诱导多能干细胞 (iPSC),将其分化为神经元. 基因表达分析揭示了显著的差异,确定了精准医学潜在的疾病亚型.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 诱导多能干细胞 (iPSC) 为研究阿尔茨海默氏症 (AD) 等疾病提供了一个模型,没有混因素.
- 干细胞技术的进步使得患者特定的细胞类型可以用于疾病建模.
研究的目的:
- 为了生成和分析来自阿尔茨海默病 (AD) 患者和健康对照者的iPSCs.
- 与对照人群相比,确定来自AD患者的神经元的转录组差异.
- 基于基因表达模式,探索AD内的潜在生物亚型.
主要方法:
- 从8名阿尔茨海默病患者和6名对照人群中生成iPSCs.
- iPSCs在激发性谷氨酸性神经元中的lentiviral分化.
- RNA测序和比较转录组分析.
- 生物信息分析包括统一的多重近似和投影 (UMAP).
主要成果:
- 在AD和对照神经元之间确定了621个不同表达的基因 (调整后p<0.05).
- 发现与现有的AD转录组研究有显著的重叠和一致性.
- 在差异表达集合中从全基因组关联研究中发现了五个AD相关基因.
- 通过STRING数据库分析观察到这些基因之间的蛋白质-蛋白质相互作用的丰富.
- 基于基因表达的UMAP分析表明了不同的患者群,可能与临床差异相关.
结论:
- 患者衍生的iPSC衍生的神经元在阿尔茨海默病中显示出不同的分子特征.
- 基因表达模式突出显示潜在的功能网络,并识别AD相关基因.
- 显著的转录组集群表明,在AD中存在临床相关的生物亚型.
- 这些发现为精准医学在阿尔茨海默病治疗中的方法铺平了道路.
更多相关视频
10:53Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions
Published on: November 9, 2020
4.9K
11:52Establishment of an Electrophysiological Platform for Modeling ALS with Regionally-Specific Human Pluripotent Stem Cell-Derived Astrocytes and Neurons
Published on: August 26, 2021
2.3K
相关概念视频
01:21EPS and iPS Cells in Disease Research
2.8K
Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
2.8K
01:22iPS Cell Differentiation
2.7K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.7K
01:13Induced Pluripotent Stem Cells
24.2K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
24.2K