AD文献阅读第5期：Science—星形胶质细胞研究重磅：科学家发现了决定健康和疾病状态下星形胶质细胞形态的基因网络

中文摘要

星形胶质细胞是一种胶质细胞，它是一种数量丰富、形态复杂的细胞。在这里，研究人员报告了小鼠中枢神经系统（CNS）中星形胶质细胞的分子分布、多样性和形态学。他们鉴定了共享的和区域特异性的星形胶质细胞基因和功能，并探讨了它们区域多样性的细胞起源。他们确定了与星形胶质细胞形态相关的基因网络，其中一些意外地包含阿尔茨海默病（AD）风险基因。CRISPR/Cas9介导的候选基因的减少降低了星形胶质细胞的形态学复杂性，并导致认知缺陷。在星形胶质细胞形态减少的人类AD、AD小鼠模型以及其他人类大脑疾病中，同样的基因出现了下调。因此，他们提供了中枢神经系统星形胶质细胞多样性和机制的全面分子数据，以及健康和疾病中星形胶质细胞形态的分子基础。

英文摘要

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer's disease (AD) risk genes. CRISPR/Cas9-mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.

参考文献：Molecular basis of astrocyte diversity and morphology across the CNS in health and disease. Science. 2022 Nov 4;378(6619):eadc9020. doi: 10.1126/science.adc9020. Epub 2022 Nov 4.

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