Supported by the National Natural Science Foundation of China (Grant No. 32425024), the research team led by Prof. Li Hanjie, from the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, in collaboration with Chen Yun from Nanjing Medical University, has made progress in research on microglia evolution. The research results were published online in Cell on April 7, 2025, titled "Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution" (Paper link: https://doi.org/10.1016/j.cell.2025.02.007).

As a crucial component of the immune system, macrophages are widely distributed across various tissues and organs, playing a key role in embryonic development, organ formation, homeostasis maintenance, and the onset and progression of diseases. Macrophage subpopulations are diverse and have complex functions. Microglia, as a specialized member of the macrophage subpopulations, are widely involved in both physiological and pathological processes, including immune surveillance and inflammatory responses, neurodevelopment and neurodegenerative diseases in the central nervous system (CNS). However, due to the extensive application of rodent models, it was previously believed that microglia did not exist in the peripheral nervous system (PNS).

The research team led by Li Hanjie utilized single-cell transcriptomics, epigenetics, characteristic protein expression, and developmental origins to identify, for the first time, a population of microglia in the PNS that are associated with species’ body size and enwrap neuronal cell bodies. Further functional studies revealed the crucial role of PNS microglia in neuronal cell body enlargement, axon growth, and functional maturation. Additionally, a multi-species systematic evolutionary analysis demonstrated that PNS microglia have ancient origins and are positively correlated with both species body size and the size of peripheral neuronal cell bodies, thereby confirming the previously mentioned findings regarding the role of PNS microglia in regulating neuronal function (Figure).

This study not only proposes a new immune-neural interaction model but also enhances our understanding of the distribution and function of microglia. The discovery of PNS microglia challenges the century-old belief that microglia are exclusively found in the CNS and provides a new perspective for the study of PNS development and related diseases.

Figure: The ontogeny, function and evolution of peripheral nervous system microglia.