在体外神经发育过程中,细胞形态和基因表达的联合分析
Adithi Sundaresh1, Dimitri Meistermann1, Riina Lampela1
1Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
eLife
|December 1, 2025
概括
这项研究整合了细胞绘画和单细胞RNA测序,以使用诱导多能干细胞 (iPSC) 建模人类神经发育. 这些发现揭示了与大脑疾病相关的细胞表型,并突出了iPSC衍生的神经元作为有价值的疾病模型.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 基因组学就是基因组学.
背景情况:
- 诱导多能干细胞 (iPSCs) 对于模拟人类神经发育和疾病至关重要.
- 了解神经元分化需要详细的细胞和分子概况.
研究的目的:
- 在iPSC衍生的皮层神经元中共同分析神经元形态和基因表达.
- 在神经元分化过程中模拟形态和基因表达之间的关系.
- 确定与神经发育和精神疾病相关的细胞表型.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和细胞绘制 (CP) 用于描述6万个iPSC衍生的皮质神经元.
- 在三个发育时间点应用了多模式单细胞分析.
- 机器学习模型被用来将形态特征与基因表达数据联系起来.
主要成果:
- 细胞绘画解决了比scRNA-seq更广泛的神经元类,并量化了线粒体功能和细胞周期等差异化驱动因素.
- 超过60%的细胞类似于胎儿大脑神经元,而28%的细胞表现出异常的代谢状态或体外特定类.
- 对诸如精神分裂症和双相情感障碍等特征的疾病遗传性被捕获在形态特征空间中.
- 卡布基综合征患者衍生细胞显示出早期分化和改变细胞循环的形态特征.
结论:
- 对iPSC衍生神经元的多模单细胞表征提供了对细胞和分子表型的互补见解.
- 来自iPSC的皮质神经元作为复杂的大脑相关特征的相关模型.
- 细胞绘画与scRNA-seq相结合,增强了对神经元分化和疾病建模的理解.
相关概念视频
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Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
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