论文
论文标题：Pyramidal neuron subtype diversity governs microglia states in the neocortex
作者：Jeffrey A. Stogsdill, Kwanho Kim, Loïc Binan, Samouil L. Farhi, Joshua Z. Levin & Paola Arlotta
期刊：Nature
发表时间：2022/08/10
数字识别码：10.1038/s41586-022-05056-7
摘要：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.
2022年8月10日，哈佛大学干细胞和再生生物学系Paola Arlotta团队在Nature杂志发表了文章 Pyramidal neuron subtype diversity governs microglia states in the neocortex 。借助单细胞和空间转录组分析，研究发现新皮层内小胶质细胞的状态及其分布是由附近的特定亚型的投射神经元（PN）所决定，并且这种神经元-小胶质细胞之间的交流是由双向配体-受体相互作用所介导的。
1. Prinz, M., S. Jung, and J. Priller, Microglia Biology: One Century of Evolving Concepts. Cell, 2019. 179(2): p. 292-311.
2. Bennett, F.C., et al., A Combination of Ontogeny and CNS Environment Establishes Microglial Identity. Neuron, 2018. 98(6).
3. De Biase, L.M., et al., Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia. Neuron, 2017. 95(2).
