Recent advances of single-cell sequencing technology in microglia phenotypic heterogeneity research

doi:10.3877/cma.j.issn.2095-9141.2021.03.007

Abstract

Abstract:

Microglia (MG) are the innate macrophages in the central nervous system (CNS) that play a key role in the processes of development and adulthood of the nervous system. Although MG have been shown to manifest significant phenotypical heterogeneity, which allows them to make a wide range of responses to environmental change for the maintenance of CNS homeostasis. So far, an effective and unbiased and high-throughput method is still lacking to assess the spatial and temporal distribution heterogeneity of MG. The recent emergence of novel single-cell techniques, such as single-cell RNA sequencing and cytometry by time-of-flight mass spectrometry, have greatly promoted our understanding of MG heterogeneity. This article reviews the current knowledge about single-cell sequencing technology in MG heterogeneity research.

Key words: Microglia, Central nervous system, Phenotypical heterogeneity, Single-cell RNA sequencing, Cytometry by time-of-flight mass spectrometry

Lin Cai, Qiuyuan Gong, Wei Wang, Hengli Tian. Recent advances of single-cell sequencing technology in microglia phenotypic heterogeneity research[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2021, 07(03): 156-160.

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References 48

[1]	Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease[J]. Nat Rev Neurosci, 2014, 15(5): 300-312.
[2]	Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration[J]. Annu Rev Immunol, 2017, 35: 441-468.
[3]	Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts[J]. Cell, 2019, 179(2): 292-311.
[4]	Lawson LJ, Perry VH, Dri P, et al. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain[J]. Neuroscience, 1990, 39(1): 151-170.
[5]	Gomez Perdiguero E, Klapproth K, Schulz C, et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors[J]. Nature, 2015, 518(7540): 547-551.
[6]	Hoeffel G, Ginhoux F. Ontogeny of tissue-resident macrophages[J]. Front Immunol, 2015, 6: 486.
[7]	Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages[J]. Science, 2010, 330(6005): 841-845.
[8]	Abiega O, Beccari S, Diaz-Aparicio I, et al. Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling[J]. PLoS Biol, 2016, 14(5): e1002466.
[9]	Rothhammer V, Borucki DM, Tjon EC, et al. Microglial control of astrocytes in response to microbial metabolites[J]. Nature, 2018, 557(7707): 724-728.
[10]	Ueno M, Fujita Y, Tanaka T, et al. Layer V cortical neurons require microglial support for survival during postnatal development[J]. Nat Neurosci, 2013, 16(5): 543-551.
[11]	Arno B, Grassivaro F, Rossi C, et al. Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex[J]. Nat Commun, 2014, 5: 5611.
[12]	党圆圆，张洪钿，徐如祥.小胶质细胞在中枢神经系统创伤后的双重作用及调控机制[J].中华神经创伤外科电子杂志, 2016, 2(5): 305-312.
[13]	Butovsky O, Koronyo-Hamaoui M, Kunis G, et al. Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1[J]. Proc Natl Acad Sci USA, 2006, 103(31): 11784-11789.
[14]	Keren-Shaul H, Spinrad A, Weiner A, et al. A unique microglia type associated with restricting development of Alzheimer’s disease[J]. Cell, 2017, 169(7): 1276-1290.e17.
[15]	Grun D, Lyubimova A, Kester L, et al. Single-cell messenger rna sequencing reveals rare intestinal cell types[J]. Nature, 2015, 525(7568): 251-255.
[16]	Mrdjen D, Pavlovic A, Hartmann FJ, et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease[J]. Immunity, 2018, 48(3): 599.
[17]	Bottcher C, Schlickeiser S, Sneeboer MAM, et al. Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry[J]. Nature neurosci, 2019, 22(1): 78-90.
[18]	Prinz M, Erny D, Hagemeyer N. Ontogeny and homeostasis of CNS myeloid cells[J]. Nat Immunol, 2017, 18(4): 385-392.
[19]	Goldmann T, Wieghofer P, Jordao MJ, et al. Origin, fate and dynamics of macrophages at central nervous system interfaces[J]. Nat Immunol, 2016, 17(7): 797-805.
[20]	Jordao MJC, Sankowski R, Brendecke SM, et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation[J]. Science, 2019, 363(6425): eaat7554.
[21]	Utz SG, See P, Mildenberger W, et al. Early fate defines microglia and non-parenchymal brain macrophage development[J]. Cell, 2020, 181(3): 557-573. e18.
[22]	Arnold TD, Lizama CO, Cautivo KM, et al. Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction[J]. J Exp Med, 2019, 216(4): 900-915.
[23]	Mazaheri F, Breus O, Durdu S, et al. Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia[J]. Nat Commun, 2014, 5: 4046.
[24]	Frost JL, Schafer DP. Microglia: architects of the developing nervous system[J]. Trends in cell biology, 2016, 26(8): 587-597.
[25]	Mildner A, Schmidt H, Nitsche M, et al. Microglia in the adult brain arise from ly-6chiccr2+ monocytes only under defined host conditions[J]. Nat Neurosci, 2007, 10(12): 1544-1553.
[26]	Ayata P, Badimon A, Strasburger HJ, et al. Epigenetic regulation of brain region-specific microglia clearance activity[J]. Nature Neurosci, 2018, 21(8): 1049-1060.
[27]	Menassa DA, Gomez-Nicola D. Microglial dynamics during human brain development[J]. Front Immunol, 2018, 9: 1014.
[28]	Goldmann T, Zeller N, Raasch J, et al. Usp18 lack in microglia causes destructive interferonopathy of the mouse brain[J]. EMBO J, 2015, 34(12): 1612-1629.
[29]	Hammond TR, Dufort C, Dissing-Olesen L, et al. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes[J]. Immunity, 2019, 50(1): 253-271. e6.
[30]	Li Q, Cheng Z, Zhou L, et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing[J]. Neuron, 2019, 101(2): 207-223. e10.
[31]	Masuda T, Sankowski R, Staszewski O, et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution[J]. Nature, 2019, 566(7744): 388-392.
[32]	Hagemeyer N, Hanft KM, Akriditou MA, et al. Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood[J]. Acta neuropathologica, 2017, 134(3): 441-458.
[33]	Krasemann S, Madore C, Cialic R, et al. The trem2-apoe pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases[J]. Immunity, 2017, 47(3): 566-581 e569.
[34]	Grabert K, Michoel T, Karavolos MH, et al. Microglial brain region-dependent diversity and selective regional sensitivities to aging[J]. Nature neuroscience, 2016, 19(3): 504-516.
[35]	Guneykaya D, Ivanov A, Hernandez DP, et al. Transcriptional and translational differences of microglia from male and female brains[J]. Cell Rep, 2018, 24(10): 2773-2783. e6.
[36]	Liddelow SA, Guttenplan KA, Clarke LE, et al. Neurotoxic reactive astrocytes are induced by activated microglia[J]. Nature, 2017, 541(7638): 481-487.
[37]	Sousa C, Golebiewska A, Poovathingal SK, et al. Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures[J]. EMBO reports, 2018, 19(11): e46171.
[38]	Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression[J]. Nat Neurosci, 2016, 19(1): 20-27.
[39]	Galatro TF, Holtman IR, Lerario AM, et al. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes[J]. Nat Neurosci, 2017, 20(8): 1162-1171.
[40]	Zhong S, Zhang S, Fan X, et al. A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex[J]. Nature, 2018, 555(7697): 524-528.
[41]	Colonna M, Brioschi S. Neuroinflammation and neurodegeneration in human brain at single-cell resolution[J]. Nat Rev Immunol, 2020, 20(2): 81-82.
[42]	Gosselin D, Skola D, Coufal NG, et al. An environment-dependent transcriptional network specifies human microglia identity[J]. Science, 2017, 356(6344): eaal3222.
[43]	Darmanis S, Sloan SA, Zhang Y, et al. A survey of human brain transcriptome diversity at the single cell level[J]. Proc Natl Acad Sci USA, 2015, 112(23): 7285-7290.
[44]	Sankowski R, Bottcher C, Masuda T, et al. Mapping microglia states in the human brain through the integration of high-dimensional techniques[J]. Nat Neurosci, 2019, 22(12): 2098-2110.
[45]	Salter MW, Stevens B. Microglia emerge as central players in brain disease[J]. Nat Med, 2017, 23(9): 1018-1027.
[46]	Benmamar-Badel A, Owens T, Wlodarczyk A. Protective microglial subset in development, aging, and disease: lessons from transcriptomic studies[J]. Front Immunol, 2020, 11: 430.
[47]	Faissner S, Plemel JR, Gold R, et al. Progressive multiple sclerosis: from pathophysiology to therapeutic strategies[J]. Nat Rev Drug Discov, 2019, 18(12): 905-922.
[48]	Stoeckius M, Hafemeister C, Stephenson W, et al. Simultaneous epitope and transcriptome measurement in single cells[J]. Nat Methods, 2017, 14(9): 865-868.

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