小柯机器人

美国哈佛大学Paola Arlotta团队发现，锥体神经元亚型多样性支配着新皮层中的小胶质细胞状态。2022年8月10日，《自然》杂志在线发表了这一最新研究成果。

研究人员使用小鼠体感皮层，证明小胶质细胞的密度和分子状态的获得是由锥体神经元类别的局部组成决定的。利用单细胞和空间转录组分析，研究人员揭示了不同小胶质细胞群的分子特征和空间分布，并表明某些状态在特定的皮层中富集，而其他状态则广泛分布于整个皮层。值得注意的是，深层锥体神经元转换为另类身份时，会重新配置局部的、富含同源小胶质细胞的分布，从而匹配新的神经元微环境。利用新皮质中锥体神经元的转录多样性，研究人员构建了一个配体-受体图谱，描述了单个锥体神经元亚型和小胶质细胞状态之间的相互作用，揭示了神经元-小胶质细胞交流的规则。这些研究结果揭示了神经元多样性在指导小胶质细胞状态的获得方面的基本作用，这是一种在大脑皮层局部回路中微调神经免疫相互作用的潜在机制。

据悉，小胶质细胞是脑实质中专门的巨噬细胞，以多种转录状态存在，并居住在广泛的神经元环境中。然而，这些状态是如何以及在哪里产生的，人们仍然不甚了解。

附：英文原文

Title: Pyramidal neuron subtype diversity governs microglia states in the neocortex

Author: Stogsdill, Jeffrey A., Kim, Kwanho, Binan, Loc, Farhi, Samouil L., Levin, Joshua Z., Arlotta, Paola

Issue&Volume: 2022-08-10

Abstract: Microglia are specialized macrophages in the brain parenchyma that exist in multiple transcriptional states and reside within a wide range of neuronal environments1,2,3,4. However, how and where these states are generated remains poorly understood. Here, using the mouse somatosensory cortex, we demonstrate that microglia density and molecular state acquisition are determined by the local composition of pyramidal neuron classes. Using single-cell and spatial transcriptomic profiling, we unveil the molecular signatures and spatial distributions of diverse microglia populations and show that certain states are enriched in specific cortical layers, whereas others are broadly distributed throughout the cortex. Notably, conversion of deep-layer pyramidal neurons to an alternate class identity reconfigures the distribution of local, layer-enriched homeostatic microglia to match the new neuronal niche. Leveraging the transcriptional diversity of pyramidal neurons in the neocortex, we construct a ligand–receptor atlas describing interactions between individual pyramidal neuron subtypes and microglia states, revealing rules of neuron–microglia communication. Our findings uncover a fundamental role for neuronal diversity in instructing the acquisition of microglia states as a potential mechanism for fine-tuning neuroimmune interactions within the cortical local circuitry.

DOI: 10.1038/s41586-022-05056-7

Source: https://www.nature.com/articles/s41586-022-05056-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html