美国洛克菲勒大学Junyue Cao和Wei Zhou团队的研究全面解析了人和小鼠大脑中与衰老和阿尔茨海默症发病相关的细胞群动态和分子特征。该研究于2023年11月30日发表于国际学术期刊《自然—遗传学》杂志。

研究人员研发了一种先进的单细胞组合索引策略-EasySci，用于探索哺乳动物大脑中与年龄相关的细胞动态。通过分析不同小鼠大脑中约150万个单细胞转录组和40万个染色质可及性图谱，研究确定了300多种细胞亚型，并揭示了它们的分子特征和空间位置。这种全面的分析阐明了衰老时增加或减少的罕见细胞类型。研究人员还探究了细胞类型对与阿尔茨海默病有关基因改变的特异性反应，确定了相关的稀有细胞类型。

此外，通过分析118,240个人脑单细胞转录组，研究发现了与阿尔茨海默病发病机制相关的细胞和区域特异性转录组变化。总之，该研究为探究正常和病理性衰老过程中细胞类型特异性动态提供了宝贵的资源。

据了解，传统方法无法揭示与衰老和疾病有关罕见细胞类型的动态变化。

附：英文原文

Title: A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains

Author: Sziraki, Andras, Lu, Ziyu, Lee, Jasper, Banyai, Gabor, Anderson, Sonya, Abdulraouf, Abdulraouf, Metzner, Eli, Liao, Andrew, Banfelder, Jason, Epstein, Alexander, Schaefer, Chloe, Xu, Zihan, Zhang, Zehao, Gan, Li, Nelson, Peter T., Zhou, Wei, Cao, Junyue

Issue&Volume: 2023-11-30

Abstract: Conventional methods fall short in unraveling the dynamics of rare cell types related to aging and diseases. Here we introduce EasySci, an advanced single-cell combinatorial indexing strategy for exploring age-dependent cellular dynamics in the mammalian brain. Profiling approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles across diverse mouse brains, we identified over 300 cell subtypes, uncovering their molecular characteristics and spatial locations. This comprehensive view elucidates rare cell types expanded or depleted upon aging. We also investigated cell-type-specific responses to genetic alterations linked to Alzheimer’s disease, identifying associated rare cell types. Additionally, by profiling 118,240 human brain single-cell transcriptomes, we discerned cell- and region-specific transcriptomic changes tied to Alzheimer’s pathogenesis. In conclusion, this research offers a valuable resource for probing cell-type-specific dynamics in both normal and pathological aging.

DOI: 10.1038/s41588-023-01572-y

Source: https://www.nature.com/articles/s41588-023-01572-y