小柯机器人

近日，美国哈佛大学庄小威等研究人员合作揭示单细胞分辨率下小鼠大脑衰老的分子和空间特征。2022年12月28日，国际知名学术期刊《细胞》在线发表了这一成果。

研究人员使用空间分辨率的单细胞转录组学生成了额叶皮层和纹状体内的大脑衰老高分辨率细胞图谱，并量化了这些区域的主要细胞类型在小鼠生命周期内的基因表达和空间组织的变化。研究人员观察到非神经元细胞的细胞状态、基因表达和空间组织的变化比神经元要明显得多。这个数据揭示了衰老过程中胶质和免疫细胞激活的分子和空间特征，特别是在皮层下白质中富集，并确定了衰老和系统性炎症挑战引起的细胞激活模式的相似性和明显差异。这些结果为大脑中与年龄相关的衰退和炎症提供了关键性的见解。

据悉，大脑中细胞的多样性和复杂的组织阻碍了对其细胞和分子结构中与年龄有关的变化的系统性描述，也限制了人们理解衰老过程中功能下降机制的能力。

附：英文原文

Title: Molecular and spatial signatures of mouse brain aging at single-cell resolution

Author: William E. Allen, Timothy R. Blosser, Zuri A. Sullivan, Catherine Dulac, Xiaowei Zhuang

Issue&Volume: 2022-12-28

Abstract: The diversity and complex organization of cells in the brain have hindered systematic characterization of age-related changes in its cellular and molecular architecture, limiting our ability to understand the mechanisms underlying its functional decline during aging. Here, we generated a high-resolution cell atlas of brain aging within the frontal cortex and striatum using spatially resolved single-cell transcriptomics and quantified changes in gene expression and spatial organization of major cell types in these regions over the mouse lifespan. We observed substantially more pronounced changes in cell state, gene expression, and spatial organization of non-neuronal cells over neurons. Our data revealed molecular and spatial signatures of glial and immune cell activation during aging, particularly enriched in the subcortical white matter, and identified both similarities and notable differences in cell-activation patterns induced by aging and systemic inflammatory challenge. These results provide critical insights into age-related decline and inflammation in the brain.

DOI: 10.1016/j.cell.2022.12.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01523-9