Molecular basis of astrocyte diversity and morphology across the CNS in health and disease.

Molecular basis of astrocyte diversity and morphology across the CNS in health and disease.
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在健康和疾病中,星形胶质细胞多样性和形态的分子基础。

DOI:
10.1126/science.adc9020
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发表时间:
2022-11-04
期刊:
Science (New York, N.Y.)
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其他
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星形胶质细胞是一类数量丰富、形态复杂的神经胶质细胞。在这里,我们报告星形胶质细胞的分子概况,多样性和形态在小鼠中枢神经系统。我们确定了共同的和区域特异性的星形胶质细胞基因和功能,并探讨了其区域多样性的细胞起源。我们确定了与星形胶质细胞形态相关的基因网络,其中几个意外地包含阿尔茨海默病(AD)风险基因。CRISPR/Cas9介导的候选基因减少降低了星形胶质细胞的形态复杂性,并导致认知缺陷。相同的基因在人类AD、显示星形胶质细胞形态减少的AD小鼠模型和其他人类脑部疾病中下调。因此,我们提供了全面的分子数据,星形胶质细胞的多样性和机制在中枢神经系统,并在健康和疾病的星形胶质细胞形态的分子基础。我们报告了星形胶质细胞多样性的分子基础及其在健康和中枢神经系统疾病中的复杂形态。
Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse 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 downregulated 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. We report the molecular basis of astrocyte diversity and of their complex morphology in health and in CNS disorders.
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