Acknowledgement
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR20C0021) and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (grant number: 2021R1C1C1013710).
References
- Ling EA, Ng YK, Wu CH, Kaur C. Microglia: its development and role as a neuropathology sensor. Prog Brain Res 2001;132:61-79. https://doi.org/10.1016/S0079-6123(01)32066-6
- Colton CA. Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 2009;4:399-418. https://doi.org/10.1007/s11481-009-9164-4
- Dickson DW, Lee SC, Mattiace LA, Yen SH, Brosnan C. Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 1993;7:75-83. https://doi.org/10.1002/glia.440070113
- Cacabelos R, Alvarez XA, Fernandez-Novoa L, Franco A, Mangues R, Pellicer A, et al. Brain interleukin-1 beta in Alzheimer's disease and vascular dementia. Methods Find Exp Clin Pharmacol 1994;16:141-151.
- Bauer J, Konig G, Strauss S, Jonas U, Ganter U, Weidemann A, et al. In-vitro matured human macrophages express Alzheimer's beta A4-amyloid precursor protein indicating synthesis in microglial cells. FEBS Lett 1991;282:335-340. https://doi.org/10.1016/0014-5793(91)80508-Z
- Park KW, Lee HG, Jin BK, Lee YB. Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo. Exp Mol Med 2007;39:812-819. https://doi.org/10.1038/emm.2007.88
- Zhou X, Spittau B, Krieglstein K. TGFbeta signalling plays an important role in IL4-induced alternative activation of microglia. J Neuroinflammation 2012;9:210.
- Kawahara K, Suenobu M, Yoshida A, Koga K, Hyodo A, Ohtsuka H, et al. Intracerebral microinjection of interleukin-4/interleukin-13 reduces beta-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice. Neuroscience 2012;207:243-260. https://doi.org/10.1016/j.neuroscience.2012.01.049
- Bellesi M, de Vivo L, Chini M, Gilli F, Tononi G, Cirelli C. Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex. J Neurosci 2017;37:5263-5273. https://doi.org/10.1523/JNEUROSCI.3981-16.2017
- Bisht K, Sharma K, Tremblay ME. Chronic stress as a risk factor for Alzheimer's disease: roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiol Stress 2018;9:9-21. https://doi.org/10.1016/j.ynstr.2018.05.003
- Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 2015;18:965-977. https://doi.org/10.1038/nn.4030
- Madore C, Yin Z, Leibowitz J, Butovsky O. Microglia, lifestyle stress, and neurodegeneration. Immunity 2020;52:222-240. https://doi.org/10.1016/j.immuni.2019.12.003
- Zheng J, Ru W, Adolacion JR, Spurgat MS, Liu X, Yuan S, et al. Single-cell RNA-seq analysis reveals compartment-specific heterogeneity and plasticity of microglia. iScience 2021;24:102186.
- Olah M, Menon V, Habib N, Taga MF, Ma Y, Yung CJ, et al. Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer's disease. Nat Commun 2020;11:6129.
- Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, et al. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 2019;50:253-271. https://doi.org/10.1016/j.immuni.2018.11.004
- Jordao MJ, Sankowski R, Brendecke SM, Locatelli G, Tai YH, et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 2019;363:eaat7554.
- Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. Landscape of transcription in human cells. Nature 2012;489:101-108. https://doi.org/10.1038/nature11233
- Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012;22:1775-1789. https://doi.org/10.1101/gr.132159.111
- Mattick JS, Makunin IV. Non-coding RNA. Hum Mol Genet 2006;15 Spec No 1:R17-R29. https://doi.org/10.1093/hmg/ddl046
- Lee KT, Nam JW. Post-transcriptional and translational regulation of mRNA-like long non-coding RNAs by microRNAs in early developmental stages of zebrafish embryos. BMB Rep 2017;50:226-231. https://doi.org/10.5483/BMBRep.2017.50.4.025
- Mourtada-Maarabouni M, Hedge VL, Kirkham L, Farzaneh F, Williams GT. Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5). J Cell Sci 2008;121:939-946. https://doi.org/10.1242/jcs.024646
- Reeves MB, Davies AA, McSharry BP, Wilkinson GW, Sinclair JH. Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science 2007;316:1345-1348. https://doi.org/10.1126/science.1142984
- Sheik Mohamed J, Gaughwin PM, Lim B, Robson P, Lipovich L. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 2010;16:324-337. https://doi.org/10.1261/rna.1441510
- Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 2010;42:1113-1117. https://doi.org/10.1038/ng.710
- Zhang X, Zhu XL, Ji BY, Cao X, Yu LJ, Zhang Y, et al. LncRNA-1810034E14Rik reduces microglia activation in experimental ischemic stroke. J Neuroinflammation 2019;16:75.
- Sun D, Yu Z, Fang X, Liu M, Pu Y, Shao Q, et al. LncRNA GAS5 inhibits microglial M2 polarization and exacerbates demyelination. EMBO Rep 2017;18:1801-1816. https://doi.org/10.15252/embr.201643668
- Shao M, Jin M, Xu S, Zheng C, Zhu W, Ma X, et al. Exosomes from long noncoding RNA-Gm37494-ADSCs repair spinal cord injury via shifting microglial M1/M2 polarization. Inflammation 2020;43:1536-1547. https://doi.org/10.1007/s10753-020-01230-z
- Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014;30:2114-2120. https://doi.org/10.1093/bioinformatics/btu170
- Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 2013;29:15-21. https://doi.org/10.1093/bioinformatics/bts635
- Liao Y, Smyth GK, Shi W. The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res 2013;41:e108.
- Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014;30:923-930. https://doi.org/10.1093/bioinformatics/btt656
- Frankish A, Diekhans M, Ferreira AM, Johnson R, Jungreis I, Loveland J, et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 2019;47:D766-D773. https://doi.org/10.1093/nar/gky955
- Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15:550.
- Cherry JD, Olschowka JA, O'Banion MK. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 2014;11:98.
- Masuda T, Sankowski R, Staszewski O, Bottcher C, Amann L, Sagar, et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature 2019;566:388-392. https://doi.org/10.1038/s41586-019-0924-x
- Cardoso AL, Guedes JR, Pereira de Almeida L, Pedroso de Lima MC. miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production. Immunology 2012;135:73-88. https://doi.org/10.1111/j.1365-2567.2011.03514.x
- Freilich RW, Woodbury ME, Ikezu T. Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia. PLoS One 2013;8:e79416.
- Mathy NW, Burleigh O, Kochvar A, Whiteford ER, Behrens M, Marta P, et al. A novel long intergenic non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia. J Neuroinflammation 2021;18:16.
- Wen J, Liu Y, Zhan Z, Chen S, Hu B, Ge J, et al. Comprehensive analysis of mRNAs, lncRNAs and circRNAs in the early phase of microglial activation. Exp Ther Med 2021;22:1460.
- Li B, Dasgupta C, Huang L, Meng X, Zhang L. MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy. Cell Mol Immunol 2020;17:976-991. https://doi.org/10.1038/s41423-019-0257-6
- Hadjicharalambous MR, Roux BT, Feghali-Bostwick CA, Murray LA, Clarke DL, Lindsay MA. Long non-coding RNAs are central regulators of the IL-1beta-induced inflammatory response in normal and idiopathic pulmonary lung fibroblasts. Front Immunol 2018;9:2906.
- Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci 2014;17:131-143. https://doi.org/10.1038/nn.3599
- Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X, et al. MicroRNA let7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun 2015;49:75-85. https://doi.org/10.1016/j.bbi.2015.04.014
- Liu W, Taso O, Wang R, Bayram S, Graham AC, Garcia-Reitboeck P, et al. Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions. Hum Mol Genet 2020;29:3224-3248. https://doi.org/10.1093/hmg/ddaa209
- Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature 2012;482:339-346. https://doi.org/10.1038/nature10887
- Chen H, Du G, Song X, Li L. Non-coding transcripts from enhancers: new insights into enhancer activity and gene expression regulation. Genomics Proteomics Bioinformatics 2017;15:201-207. https://doi.org/10.1016/j.gpb.2017.02.003
- Gaikwad SM, Heneka MT. Studying M1 and M2 states in adult microglia. Methods Mol Biol 2013;1041:185-197. https://doi.org/10.1007/978-1-62703-520-0_18
- Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol 2016;53:1181-1194. https://doi.org/10.1007/s12035-014-9070-5
- Xu L, He D, Bai Y. Microglia-mediated inflammation and neurodegenerative disease. Mol Neurobiol 2016;53:6709-6715. https://doi.org/10.1007/s12035-015-9593-4
- Jia H, Ma H, Li Z, Chen F, Fang B, Cao X, et al. Downregulation of lncRNA TUG1 inhibited TLR4 signaling pathway-mediated inflammatory damage after spinal cord ischemia reperfusion in rats via suppressing TRIL expression. J Neuropathol Exp Neurol 2019;78:268-282. https://doi.org/10.1093/jnen/nly126
- Sun Q, Song YJ, Prasanth KV. One locus with two roles: microRNA-independent functions of microRNA-host-gene locus-encoded long noncoding RNAs. Wiley Interdiscip Rev RNA 2021;12:e1625.
- Faraoni I, Antonetti FR, Cardone J, Bonmassar E. miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta 2009;1792:497-505. https://doi.org/10.1016/j.bbadis.2009.02.013
- Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M. Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res 2008;36:6608-6619. https://doi.org/10.1093/nar/gkn666
- Xue Z, Zhang Z, Liu H, Li W, Guo X, Zhang Z, et al. lincRNA-Cox2 regulates NLRP3 inflammasome and autophagy mediated neuroinflammation. Cell Death Differ 2019;26:130-145. https://doi.org/10.1038/s41418-018-0105-8