The microglial lineage
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Microglial lineage cells are resident immune cells characterized by a microglial molecular phenotype and ontogeny[1].They exhibit diverse tissue distribution and functions while sharing the same transcriptome, protein markers, morphology, epigenetic profiles, and developmental origin as central nervous system (CNS) microglia.[1]
History
- The definition was first proposed by Hanjie Li's group.[1] Through single-cell RNA sequencing (scRNA-seq) profiling of various human fetal organs/tissues during prenatal development, they and others identified a peripheral immune cell population displaying a microglial transcriptome.[2][3][4][5][6][7] These cells express markers P2RY12, SALL1, and TMEM119, but lack expression of MRC1, DAB2, and LYVE1. This population was found in fetal skin, testicles, heart, and the peripheral nervous system (PNS).[2][3][4][5][6][7]
Functions
- Peripheral microglial lineage cells display a remarkably diverse spatial distribution across tissues, including fetal skin, testis, heart, and the PNS.[2][8]
• Fetal Skin
- These cells localize within the epidermis and physically interact with neural crest cells, facilitating their differentiation into melanocyte precursors.[2][6][7]
• Peripheral Nervous System (PNS)
- In sensory ganglia (e.g., dorsal root ganglia, DRG) and sympathetic ganglia (SG), PNS microglia occupy the space between neuronal somata and the enveloping satellite glial cells (SGCs). They form direct physical interfaces with neuronal somata. These interactions are critical for neuronal maturation, regulating soma enlargement and axon growth. Depletion of PNS microglia impairs neuronal excitability and somatosensation.[5]
References
- ↑ 1.0 1.1 1.2 Li, H.; Chen, W. -w.; Wu, Z (2025). "The microglial lineage: present and beyond". Trends in Immunology. 46 (6): 438–440. doi:10.1016/j.it.2025.04.001. PMID 40368697 Check
|pmid=value (help). - ↑ 2.0 2.1 2.2 2.3 Li, H.; Wang, Z.; Wu, Z (2023). "An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development". Cell. 186 (20): 4454-4471. doi:10.1016/j.cell.2023.08.019. PMID 37703875 Check
|pmid=value (help). - ↑ 3.0 3.1 Gopee, N.H. (2024). "A prenatal skin atlas reveals immune regulation of human skin morphogenesis". Nature. 635 (8039): 679–689. Bibcode:2024Natur.635..679G. doi:10.1038/s41586-024-08002-x. PMC 11578897 Check
|pmc=value (help). PMID 39415002 Check|pmid=value (help). - ↑ 4.0 4.1 Garcia-Alonso, L. (2022). "Single-cell roadmap of human gonadal development". Nature. 607 (7919): 540–547. Bibcode:2022Natur.607..540G. doi:10.1038/s41586-022-04918-4. PMC 9300467 Check
|pmc=value (help). PMID 35794482 Check|pmid=value (help). - ↑ 5.0 5.1 5.2 Li, H.; Wu, Z.; Wang, Y.; Chen, W. -w.; Sun, H. (2025). "Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution". Cell. 188 (8): 2159–2174.e15. doi:10.1016/j.cell.2025.02.007. PMID 40199320 Check
|pmid=value (help). - ↑ 6.0 6.1 6.2 Suo, C. (2022). "Mapping the developing human immune system across organs". Science. 376 (6597): eabo0510. doi:10.1126/science.abo0510. PMC 7612819 Check
|pmc=value (help). PMID 35549310 Check|pmid=value (help). - ↑ 7.0 7.1 7.2 Goh, I; Botting, RA (2023). "Yolk sac cell atlas reveals multiorgan functions during human early development". Science. 381 (6659). doi:10.1126/science.add7564. PMID 37590359 Check
|pmid=value (help). - ↑ Chen, X. (2025). "Cross one single body 49 tissues single-cell transcriptome reveals detailed macrophage heterogeneity during pig pregnancy Provisionally". Front. Immunol. doi:10.3389/fimmu.2025.1574120.
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