Two Phenotypically and Functionally Distinct Microglial Populations in Adult Zebrafish

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Nov 19

PMID 33208372

Citations 33

Authors

Shuting Wu

Linh T M Nguyen

Hongru Pan

Shaoli Hassan

Yimei Dai

Jin Xu

Zilong Wen

Affiliations

Soon will be listed here.

Abstract

Microglia are the tissue-resident macrophages in the central nervous system and are critically involved in immune defense, neural development and function, and neuroinflammation. The versatility of microglia has long been attributed to heterogeneity. Recent studies have revealed possible heterogeneity in human but not in murine microglia, yet a firm demonstration linking microglial heterogeneity to functional phenotypes remains scarce. Here, we identified two distinct microglial populations in adult zebrafish that differ in morphology, distribution, development, and function. The predominant population, phagocytotic microglia, which expresses , is broadly distributed, amoeboid in shape, highly mobile, and phagocytotic. The other white matter-enriched population, regulatory microglia, has ramified protrusions but has limited mobility and phagocytosis capability. These functional differences are further supported by distinct transcriptomes and responses to bacterial infection, where microglia function in tissue clearance and microglia release immune regulators. Our study sheds light on the heterogeneity and functional diversification of microglia.

Citing Articles

Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer's disease risk genes.

Kroll F, Donnelly J, Ozcan G, Mackay E, Rihel J Elife. 2025; 13.

PMID: 39960847 PMC: 11832171. DOI: 10.7554/eLife.96839.

In Vivo Neurodynamics Mapping via High-Speed Two-Photon Fluorescence Lifetime Volumetric Projection Microscopy.

Li Y, Xu X, Zhang C, Sun X, Zhou S, Li X Adv Sci (Weinh). 2024; 12(7):e2410605.

PMID: 39716869 PMC: 11831470. DOI: 10.1002/advs.202410605.

Microglia cannibalism and efferocytosis leads to shorter lifespans of developmental microglia.

Gordon H, Schafer Z, Smith C PLoS Biol. 2024; 22(10):e3002819.

PMID: 39475879 PMC: 11524473. DOI: 10.1371/journal.pbio.3002819.

The embryonic zebrafish brain is exclusively colonized by -dependent and lymphatic-independent population of microglia.

Yu T, Chen J, Wang Y, Xu J Sci Adv. 2024; 10(35):eado0519.

PMID: 39196933 PMC: 11352844. DOI: 10.1126/sciadv.ado0519.

Bone marrow-derived myeloid cells transiently colonize the brain during postnatal development and interact with glutamatergic synapses.

Carrier M, Robert M, St-Pierre M, Gonzalez Ibanez F, de Andrade E, Laroche A iScience. 2024; 27(7):110037.

PMID: 39021809 PMC: 11253522. DOI: 10.1016/j.isci.2024.110037.

References

Tian Y, Xu J, Feng S, He S, Zhao S, Zhu L . The first wave of T lymphopoiesis in zebrafish arises from aorta endothelium independent of hematopoietic stem cells. J Exp Med. 2017; 214(11):3347-3360. PMC: 5679161. DOI: 10.1084/jem.20170488. View

Soleto I, Fischer U, Tafalla C, Granja A . Identification of a Potential Common Ancestor for Mammalian Cross-Presenting Dendritic Cells in Teleost Respiratory Surfaces. Front Immunol. 2018; 9:59. PMC: 5788898. DOI: 10.3389/fimmu.2018.00059. View

Hammond T, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A . Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes. Immunity. 2018; 50(1):253-271.e6. PMC: 6655561. DOI: 10.1016/j.immuni.2018.11.004. View

Bottcher C, Schlickeiser S, Sneeboer M, Kunkel D, Knop A, Paza E . Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. Nat Neurosci. 2018; 22(1):78-90. DOI: 10.1038/s41593-018-0290-2. View

Ransohoff R, Perry V . Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009; 27:119-45. DOI: 10.1146/annurev.immunol.021908.132528. View

Wlodarczyk A, Holtman I, Krueger M, Yogev N, Bruttger J, Khorooshi R . A novel microglial subset plays a key role in myelinogenesis in developing brain. EMBO J. 2017; 36(22):3292-3308. PMC: 5686552. DOI: 10.15252/embj.201696056. View

Ajami B, Bennett J, Krieger C, Tetzlaff W, Rossi F . Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci. 2007; 10(12):1538-43. DOI: 10.1038/nn2014. View

Li Q, Barres B . Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2017; 18(4):225-242. DOI: 10.1038/nri.2017.125. View

Verney C, Monier A, Fallet-Bianco C, Gressens P . Early microglial colonization of the human forebrain and possible involvement in periventricular white-matter injury of preterm infants. J Anat. 2010; 217(4):436-48. PMC: 2992419. DOI: 10.1111/j.1469-7580.2010.01245.x. View

10.

Wang J, Sun J, Liu L, Flies D, Nie X, Toki M . Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med. 2019; 25(4):656-666. PMC: 7175920. DOI: 10.1038/s41591-019-0374-x. View

11.

Mazaheri F, Breus O, Durdu S, Haas P, Wittbrodt J, Gilmour D . Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia. Nat Commun. 2014; 5:4046. DOI: 10.1038/ncomms5046. View

12.

Lin X, Zhou Q, Zhao C, Lin G, Xu J, Wen Z . An Ectoderm-Derived Myeloid-like Cell Population Functions as Antigen Transporters for Langerhans Cells in Zebrafish Epidermis. Dev Cell. 2019; 49(4):605-617.e5. DOI: 10.1016/j.devcel.2019.03.028. View

13.

Li Q, Cheng Z, Zhou L, Darmanis S, Neff N, Okamoto J . Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing. Neuron. 2019; 101(2):207-223.e10. PMC: 6336504. DOI: 10.1016/j.neuron.2018.12.006. View

14.

Elkabes S, Black I . Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci. 1996; 16(8):2508-21. PMC: 6578768. View

15.

Cole K, Strick C, Paradis T, Ogborne K, Loetscher M, Gladue R . Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med. 1998; 187(12):2009-21. PMC: 2212354. DOI: 10.1084/jem.187.12.2009. View

16.

Wu S, Xue R, Hassan S, Nguyen T, Wang T, Pan H . Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors. Dev Cell. 2018; 46(5):552-563.e4. DOI: 10.1016/j.devcel.2018.08.005. View

17.

Picelli S, Faridani O, Bjorklund A, Winberg G, Sagasser S, Sandberg R . Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc. 2014; 9(1):171-81. DOI: 10.1038/nprot.2014.006. View

18.

Peri F, Nusslein-Volhard C . Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell. 2008; 133(5):916-27. DOI: 10.1016/j.cell.2008.04.037. View

19.

Pont-Lezica L, Beumer W, Colasse S, Drexhage H, Versnel M, Bessis A . Microglia shape corpus callosum axon tract fasciculation: functional impact of prenatal inflammation. Eur J Neurosci. 2014; 39(10):1551-7. DOI: 10.1111/ejn.12508. View

20.

Hagemeyer N, Hanft K, Akriditou M, Unger N, Park E, Stanley E . Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood. Acta Neuropathol. 2017; 134(3):441-458. PMC: 5951721. DOI: 10.1007/s00401-017-1747-1. View