Cx3cr1- deficient microglia exhibit a premature aging transcriptome
Open accessAbstract
CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1- deficient microglia under varying conditions by RNA-sequencing (RNA-seq). In 2-mo-old mice, Cx3cr1 deletion resulted in the down-regulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1- deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1- sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a comparable fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1 -deficient mice useful for studying aged microglia.
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NOX1 expression may be an artefact of the Cx3cr1-EGFP reporter line.
“NOX1 expression may be an artefact of the Cx3cr1-EGFP reporter line, since Cx3cr1 is a signature microglial gene and haploinsufficiency has wide-reaching effects on gene expression of microglia, specifically encouraging a prematurely aged transcriptome [78,79,80].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [78]
This expression profile concurs with other studies of DAM.
“This expression profile concurs with other studies of DAM [10,37,78,124,194].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [78]
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 3× · see citing works
“DESeq2 (Love et al, 2014) was used to identify differential chromatin binding between Cx3cr1 -KO and -WT mice.”
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · cited 1× · see citing works
“The raw Rbp2 or H3K27Ac ChIP sequences were mapped to mm10 genome by Bowtie 2 (Langmead & Salzberg, 2013).”
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 2× · see citing works
“Raw count fi les were aligned to mouse genome build mm10 using STAR and transcripts quanti fi ed with RSEM; in general, the uniquemappingratewas>80%.”
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · cited 2× · see citing works
“ChIP-seq library preparation, sequencing, and data analysis ChIP-seq libraries were prepared from recovered DNA by blunting, A-tailing, and adapter ligation using barcoded adapters (NextFlex; Bioo Scienti fi c) as previously described (Heinz et al, 2010; Gosselin et al, 2014).”
Self-citationComplex heatmaps reveal patterns and correlations in multidimensional genomic data
Gu, Z., Eils, R., & Schlesner, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw313 · Cited by 10,122 · cited 1× · see citing works
“Heatmap visualizations of the DEGs were made by using custom R scripts based on ComplexHeatmap (Gu et al, 2016).”
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · cited 1× · see citing works
“In multiple conditions, mouse microglia demonstrate a core conserved reactive-state transcriptome, which is extensively modi fi ed to yield disease-speci fi c transcriptomes (Chiu et al, 2013; Keren-Shaul et al, 2017; Friedman et al, 2018).”
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 1× · see citing works
“In WT mice, the microglial expression pro fi le obtained here is consistent with the published microglial transcriptomes (Table S1) (Hickman et al, 2013; Butovsky et al, 2014; Zhang et al, 2014).”
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · cited 1× · see citing works
“…Cx3cr1 expression show altered brain development during embryogenesis, dysregulated neuronal fi ring in the fi rst few weeks after birth, and abnormal results in tests designed to mimic sociopsychological behaviors (Paolicelli et al, 2011; Rogers et al, 2011; Zhan et al, 2014; Bolós et al, 2017).”
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · cited 1× · see citing works
“Indeed, Kl (Klotho) is down-regulated in Cx3cr1 -de fi cient microglia, and Klotho protein has been linked to aging and homeostatic support of brain function (Kuro-o et al, 1997).”
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · cited 1× · see citing works
“CX3CR1 is involved in intestinal macrophage sensing of the microbiota (Niess et al, 2005), and gross disruption of the microbiota can affect microglial transcriptomes (Erny et al, 2015; Thion et al, 2018a).”
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · cited 4× · see citing works
“Cx3cr1 -de fi cient mice, in which both copies of Cx3cr1 are disrupted by the gene for eGFP (Jung et al, 2000), were initially obtained from The Jackson Laboratory and then bred to maintain them on the C57Bl/6J background.”
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Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599 · cited 1× · see citing works
“Finally, because ofits high andconsistent expression, Cx3cr1 is also often used as a driver in reporter constructs, such as Cx3cr1-eGFP mice, or for Cre-mediated gene deletion (Jung et al, 2000; Goldmann et al, 2013; Parkhurst et al, 2013).”
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · see citing works
Self-citationHow neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · cited 1× · see citing works
“They support brain development and adult CNS homeostasis, functions which are often dysregulated in acute or chronic neurological conditions (Xavier et al, 2014; Casano & Peri, 2015; Ransohoff, 2016; Hickman et al, 2018; Thion et al, 2018b).”
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Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710 · cited 1× · see citing works
“They support brain development and adult CNS homeostasis, functions which are often dysregulated in acute or chronic neurological conditions (Xavier et al, 2014; Casano & Peri, 2015; Ransohoff, 2016; Hickman et al, 2018; Thion et al, 2018b).”
CX 3 CR1-Mediated Dendritic Cell Access to the Intestinal Lumen and Bacterial Clearance
Niess, J. H., Brand, S., Gu, X., Landsman, L., Jung, S., McCormick, B. A., Vyas, J. M., Boes, M. L., Ploegh, H. L., Fox, J. G., et al. (2005) · Science · doi:10.1126/science.1102901 · Cited by 1,609 · cited 1× · see citing works
“CX3CR1 is involved in intestinal macrophage sensing of the microbiota (Niess et al, 2005), and gross disruption of the microbiota can affect microglial transcriptomes (Erny et al, 2015; Thion et al, 2018a).”
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · cited 4× · see citing works
“…in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson ’ s disease and in tauopathies such as frontotemporal dementia, but promotes amyloid clearance in models of amyloid β deposition (Cardona et al, 2006; Bhaskar et al, 2010; Lee et al, 2010; Liu et al, 2010).”
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Hickman, S. E., Kingery, N. D., Ohsumi, T. K., Borowsky, M. L., Wang, L.-C., Means, T. K., & El Khoury, J. (2013) · Nature Neuroscience · doi:10.1038/nn.3554 · Cited by 1,511 · cited 1× · see citing works
“In WT mice, the microglial expression pro fi le obtained here is consistent with the published microglial transcriptomes (Table S1) (Hickman et al, 2013; Butovsky et al, 2014; Zhang et al, 2014).”
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Sorge, R. E., Mapplebeck, J. C. S., Rosen, S., Beggs, S., Taves, S., Alexander, J. K., Martin, L. J., Austin, J.-S., Sotocinal, S. G., Chen, D., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4053 · Cited by 1,442 · cited 1× · see citing works
“…and neurodegenerative conditions and the emerging importance of gender differences in the role of microglia in response to multiple perturbations (Sorge et al, 2015; Hanamsagar et al, 2017; Thion et al, 2018a), an in-depth examination of gender differences is warranted, but beyond the scope of…”
Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307 · cited 2× · see citing works
“ChIP-seq library preparation, sequencing, and data analysis ChIP-seq libraries were prepared from recovered DNA by blunting, A-tailing, and adapter ligation using barcoded adapters (NextFlex; Bioo Scienti fi c) as previously described (Heinz et al, 2010; Gosselin et al, 2014).”
Self-citationZhan, Y., Paolicelli, R. C., Sforazzini, F., Weinhard, L., Bolasco, G., Pagani, F., Vyssotski, A. L., Bifone, A., Gozzi, A., Ragozzino, D., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3641 · Cited by 1,236 · cited 1× · see citing works
“…Cx3cr1 expression show altered brain development during embryogenesis, dysregulated neuronal fi ring in the fi rst few weeks after birth, and abnormal results in tests designed to mimic sociopsychological behaviors (Paolicelli et al, 2011; Rogers et al, 2011; Zhan et al, 2014; Bolós et al, 2017).”
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Grabert, K., Michoel, T., Karavolos, M. H., Clohisey, S., Baillie, J. K., Stevens, M. P., Freeman, T. C., Summers, K. M., & McColl, B. W. (2016) · Nature Neuroscience · doi:10.1038/nn.4222 · Cited by 1,151 · cited 4× · see citing works
“The transcriptome of young Cx3cr1 -de fi cient mice resembles that of aged WT mice Age is the dominant risk factor for neurodegenerative diseases and also alters the microglial transcriptome both in mice and humans (Grabert et al, 2016; Olah et al, 2018).”
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Li, Q., Brown, J. B., Huang, H., & Bickel, P. J. (2011) · The Annals of Applied Statistics · doi:10.1214/11-aoas466 · Cited by 1,008 · cited 3× · see citing works
“Moreover, Tnf , a classical in fl ammatory gene, had higher expression in Cx3cr1 - KO microglia by RNA-seq and a trend for differential Rbp2 binding by ChIP-seq (irreproducible discovery rate [IDR] = 0.0553; Fig 2D).”
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Wendeln, A.-C., Degenhardt, K., Kaurani, L., Gertig, M., Ulas, T., Jain, G., Wagner, J., Häsler, L. M., Wild, K., Skodras, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0023-4 · Cited by 956 · cited 1× · see citing works
“This LPS injection paradigm differs from the one we used and generates a different activation status in microglia (Wendeln et al, 2018).”
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Li, Q., Brown, J. B., Huang, H., & Bickel, P. J. (2010) · UC Berkeley · Cited by 915 · see citing works
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
Thion, M. S., Low, D., Silvin, A., Chen, J., Grisel, P., Schulte-Schrepping, J., Blecher, R., Ulas, T., Squarzoni, P., Hoeffel, G., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.042 · Cited by 779 · cited 3× · see citing works
“…conditions and the emerging importance of gender differences in the role of microglia in response to multiple perturbations (Sorge et al, 2015; Hanamsagar et al, 2017; Thion et al, 2018a), an in-depth examination of gender differences is warranted, but beyond the scope of this study.”
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Goldmann, T., Wieghofer, P., Müller, P. F., Wolf, Y., Varol, D., Yona, S., Brendecke, S. M., Kierdorf, K., Staszewski, O., Datta, M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3531 · Cited by 688 · cited 1× · see citing works
“Finally, because ofits high andconsistent expression, Cx3cr1 is also often used as a driver in reporter constructs, such as Cx3cr1-eGFP mice, or for Cre-mediated gene deletion (Jung et al, 2000; Goldmann et al, 2013; Parkhurst et al, 2013).”
Friedman, B. A., Srinivasan, K., Ayalon, G., Meilandt, W. J., Lin, H., Huntley, M. A., Cao, Y., Lee, S.-H., Haddick, P. C. G., Ngu, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.066 · Cited by 662 · cited 1× · see citing works
“In multiple conditions, mouse microglia demonstrate a core conserved reactive-state transcriptome, which is extensively modi fi ed to yield disease-speci fi c transcriptomes (Chiu et al, 2013; Keren-Shaul et al, 2017; Friedman et al, 2018).”
Chiu, I. M., Morimoto, E. T. A., Goodarzi, H., Liao, J. T., O’Keeffe, S., Phatnani, H. P., Muratet, M., Carroll, M. C., Levy, S., Tavazoie, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.018 · Cited by 651 · cited 1× · see citing works
“In multiple conditions, mouse microglia demonstrate a core conserved reactive-state transcriptome, which is extensively modi fi ed to yield disease-speci fi c transcriptomes (Chiu et al, 2013; Keren-Shaul et al, 2017; Friedman et al, 2018).”
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“…in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson ’ s disease and in tauopathies such as frontotemporal dementia, but promotes amyloid clearance in models of amyloid β deposition (Cardona et al, 2006; Bhaskar et al, 2010; Lee et al, 2010; Liu et al, 2010).”
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Rogers, J. T., Morganti, J. M., Bachstetter, A. D., Hudson, C. E., Peters, M. M., Grimmig, B. A., Weeber, E. J., Bickford, P. C., & Gemma, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3667-11.2011 · Cited by 624 · cited 2× · see citing works
“In addition, lack of Cx3cr1 expression reduces adult neurogenesis in the HC and olfactory bulb, and impairs the integration of newborn neurons (Bachstetter et al, 2011; Rogers et al, 2011; Xiao et al, 2015; Sellner et al, 2016; Reshef et al, 2017).”
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Buttgereit, A., Lelios, I., Yu, X., Vrohlings, M., Krakoski, N. R., Gautier, E. L., Nishinakamura, R., Becher, B., & Greter, M. (2016) · Nature Immunology · doi:10.1038/ni.3585 · Cited by 570 · cited 1× · see citing works
“The transcription factor Sall1 is essential for the expression of microglia signature genes, which differentiate microgliafromothertissuemacrophagesandmyeloidcells(Buttgereit et al, 2016).”
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Zheng, C., & Sankoff, D. (2016) · BMC Genomics · doi:10.1186/s12864-015-2294-6 · Cited by 554 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · cited 2× · see citing works
“…in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson ’ s disease and in tauopathies such as frontotemporal dementia, but promotes amyloid clearance in models of amyloid β deposition (Cardona et al, 2006; Bhaskar et al, 2010; Lee et al, 2010; Liu et al, 2010).”
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Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S., & Colonna, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77983 · Cited by 525 · cited 1× · see citing works
“Microgliaundergosubstantialchangesin gene expression and morphology with age (Poliani et al, 2015; Grabert et al, 2016; Olah et al, 2018), but it is not known whether the changes in microglia occur as a consequence of aging or help drive the process.”
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Bennett, F. C., Bennett, M. L., Yaqoob, F., Mulinyawe, S. B., Grant, G. A., Hayden Gephart, M., Plowey, E. D., & Barres, B. A. (2018) · Neuron · doi:10.1016/j.neuron.2018.05.014 · Cited by 524 · cited 1× · see citing works
“Microglial identity is conferred by their yolk-sac origin and the brain environment (Bennett et al, 2018).”
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Olah, M., Patrick, E., Villani, A.-C., Xu, J., White, C. C., Ryan, K. J., Piehowski, P., Kapasi, A., Nejad, P., Cimpean, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02926-5 · Cited by 482 · cited 3× · see citing works
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Ayata, P., Badimon, A., Strasburger, H. J., Duff, M. K., Montgomery, S. E., Loh, Y.-H. E., Ebert, A., Pimenova, A. A., Ramirez, B. R., Chan, A. T., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0192-3 · Cited by 460 · cited 1× · see citing works
“Microglial morphologyaccessedbythe totalIba1area andcell body – associated Iba1 dendritic process area and perimeter in the cerebellum was much lower thaninthe cortex, consistentwithless rami fi ed microglia in this brain region (Ayata et al, 2018).”
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Thion, M. S., Ginhoux, F., & Garel, S. (2018) · Science · doi:10.1126/science.aat0474 · Cited by 440 · cited 3× · see citing works
“…conditions and the emerging importance of gender differences in the role of microglia in response to multiple perturbations (Sorge et al, 2015; Hanamsagar et al, 2017; Thion et al, 2018a), an in-depth examination of gender differences is warranted, but beyond the scope of this study.”
Hanamsagar, R., Alter, M. D., Block, C. S., Sullivan, H., Bolton, J. L., & Bilbo, S. D. (2017) · Glia · doi:10.1002/glia.23176 · Cited by 384 · cited 3× · see citing works
“…conditions and the emerging importance of gender differences in the role of microglia in response to multiple perturbations (Sorge et al, 2015; Hanamsagar et al, 2017; Thion et al, 2018a), an in-depth examination of gender differences is warranted, but beyond the scope of this study.”
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Bachstetter, A. D., Morganti, J. M., Jernberg, J., Schlunk, A., Mitchell, S. H., Brewster, K. W., Hudson, C. E., Cole, M. J., Harrison, J. K., Bickford, P. C., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.11.022 · Cited by 364 · cited 3× · see citing works
“In addition, lack of Cx3cr1 expression reduces adult neurogenesis in the HC and olfactory bulb, and impairs the integration of newborn neurons (Bachstetter et al, 2011; Rogers et al, 2011; Xiao et al, 2015; Sellner et al, 2016; Reshef et al, 2017).”
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Das, H., Kumar, A., Lin, Z., Patino, W. D., Hwang, P. M., Feinberg, M. W., Majumder, P. K., & Jain, M. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508235103 · Cited by 305 · cited 1× · see citing works
“Only genes with FDR < 0.05, fold change > 30%, and average expression > 4 TPM were included in the enrichment analysis. augmented up-regulation of Klf2 , among other genes, could mediate durable functional responses by microglia (Das et al, 2006; de Bruin et al, 2016; Roberts et al, 2017).”
InfluentialHanamsagar, R., Alter, M. D., Block, C. L., Sullivan, H. K., Bolton, J. L., & Bilbo, S. D. (2017) · Glia · doi:10.1002/glia.23277 · Cited by 297 · see citing works
Liu, Z., Condello, C., Schain, A., Harb, R., & Grutzendler, J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4403-10.2010 · Cited by 276 · cited 1× · see citing works
“…in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson ’ s disease and in tauopathies such as frontotemporal dementia, but promotes amyloid clearance in models of amyloid β deposition (Cardona et al, 2006; Bhaskar et al, 2010; Lee et al, 2010; Liu et al, 2010).”
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Araki, T., & Milbrandt, J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80166-x · Cited by 263 · cited 1× · see citing works
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Roberts, A. W., Lee, B. L., Deguine, J., John, S., Shlomchik, M. J., & Barton, G. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.10.006 · Cited by 261 · cited 1× · see citing works
“Only genes with FDR < 0.05, fold change > 30%, and average expression > 4 TPM were included in the enrichment analysis. augmented up-regulation of Klf2 , among other genes, could mediate durable functional responses by microglia (Das et al, 2006; de Bruin et al, 2016; Roberts et al, 2017).”
InfluentialZhang, X., Zhang, H., Li, L., Lan, H., Ren, Z., Liu, D., Wu, L., Liu, H., Jaqueth, J. S., Li, B., et al. (2016) · BMC Genomics · doi:10.1186/s12864-016-3041-3 · Cited by 218 · see citing works
Transcriptional control of microglia phenotypes in health and disease
Holtman, I. R., Skola, D., & Glass, C. K. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90604 · Cited by 218 · cited 1× · see citing works
“Thus, microglia establish and then alter their gene expression and function, based on contextual cues that modulate the activity of an enhancer landscape, primed through the action of lineage-determining transcription factors (Holtman et al, 2017).”
Self-citationLyons, A., Lynch, A. M., Downer, E. J., Hanley, R., O’Sullivan, J. B., Smith, A., & Lynch, M. A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06253.x · Cited by 202 · cited 1× · see citing works
“It has been reported that CX3CL1 mRNA and protein expression decrease in the aged rodent brain (Lyons et al, 2009; Bachstetter et al, 2011), suggesting that reduced CX3CL1-CX3CR1 signaling may contribute to the transition of microglia to an aged phenotype.”
Microglia: Multitasking Specialists of the Brain
Casano, A. M., & Peri, F. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.018 · Cited by 192 · cited 1× · see citing works
“They support brain development and adult CNS homeostasis, functions which are often dysregulated in acute or chronic neurological conditions (Xavier et al, 2014; Casano & Peri, 2015; Ransohoff, 2016; Hickman et al, 2018; Thion et al, 2018b).”
CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice
Fumagalli, S., Perego, C., Ortolano, F., & Simoni, M. G. D. (2013) · Glia · doi:10.1002/glia.22474 · Cited by 179 · cited 1× · see citing works
“In CNS disease models, mice de fi cient for only one copy of Cx3cr1 willunpredictablyeithershowphenotypessimilartoWTmice(Fumagalli et al, 2013) or intermediate between WT and KO (Lee et al, 2010; Rogers etal, 2011).”
CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α
Garré, J. M., Silva, H. M., Lafaille, J. J., & Yang, G. (2017) · Nature Medicine · doi:10.1038/nm.4340 · Cited by 130 · cited 1× · see citing works
“Furthermore, peripheral CX3CR1 can affect brain processes, such as cognition and memory (Garr´e et al, 2017).”
Opposing Effects of Membrane-Anchored CX3CL1 on Amyloid and Tau Pathologies via the p38 MAPK Pathway
Lee, S., Xu, G., Jay, T. R., Bhatta, S., Kim, K.-W., Jung, S., Landreth, G. E., Ransohoff, R. M., & Lamb, B. T. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0853-14.2014 · Cited by 123 · cited 1× · see citing works
“These fi ndings were surprising because deletion of Cx3cr1 consistently enhanced in-fl ammatory responses in CNS disease models (Cardona et al, 2006; Bhaskar et al, 2010; Lee et al, 2014).”
Self-citationTime-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury
Febinger, H. Y., Thomasy, H. E., Pavlova, M. N., Ringgold, K. M., Barf, P. R., George, A. M., Grillo, J. N., Bachstetter, A. D., Garcia, J. A., Cardona, A. E., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0386-5 · Cited by 110 · cited 1× · see citing works
“Both protective and detrimental effects have also been reported for Cx3cr1 deletion in varied models of traumatic brain injury, including at different time points in the same model (Febinger et al, 2015; Erturk etal, 2016; Zanier etal, 2016).”
Bolós, M., Perea, J. R., Terreros‐Roncal, J., Pallas‐Bazarra, N., Jurado‐Arjona, J., Ávila, J., & Llorens-Martı́n, M. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.10.002 · Cited by 109 · see citing works
The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb
Reshef, R., Kudryavitskaya, E., Shani-Narkiss, H., Isaacson, B., Rimmerman, N., Mizrahi, A., & Yirmiya, R. (2017) · eLife · doi:10.7554/elife.30809 · Cited by 108 · cited 1× · see citing works
“In addition, lack of Cx3cr1 expression reduces adult neurogenesis in the HC and olfactory bulb, and impairs the integration of newborn neurons (Bachstetter et al, 2011; Rogers et al, 2011; Xiao et al, 2015; Sellner et al, 2016; Reshef et al, 2017).”
Zanier, E. R., Marchesi, F., Ortolano, F., Perego, C., Arabian, M., Zoerle, T., Sammali, E., Pischiutta, F., & De Simoni, M.-G. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4041 · Cited by 94 · see citing works
Ertürk, A., Mentz, S., Stout, E. E., Hedehus, M., Domínguez, S. L., Neumaier, L., Krammer, F., Llovera, G., Srinivasan, K., Hansen, D. V., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1898-15.2016 · Cited by 89 · see citing works
Sellner, S., Paricio-Montesinos, R., Spieß, A., Masuch, A., Erny, D., Harsan, L. A., von Elverfeldt, D., Schwabenland, M., Biber, K. P. H., Staszewski, O., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0374-8 · Cited by 79 · cited 1× · see citing works
“In addition, lack of Cx3cr1 expression reduces adult neurogenesis in the HC and olfactory bulb, and impairs the integration of newborn neurons (Bachstetter et al, 2011; Rogers et al, 2011; Xiao et al, 2015; Sellner et al, 2016; Reshef et al, 2017).”
Fine-tuning the central nervous system: microglial modelling of cells and synapses
Xavier, A. L. R., Menezes, J. R. L., Goldman, S. A., & Nedergaard, M. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0593 · Cited by 76 · cited 2× · see citing works
“DESeq2 (Love et al, 2014) was used to identify differential chromatin binding between Cx3cr1 -KO and -WT mice.”
Rimmerman, N., Schottlender, N., Reshef, R., Dan-Goor, N., & Yirmiya, R. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.11.023 · Cited by 65 · cited 1× · see citing works
“Reassuringly, our results with isolatedmicrogliawereconsistentwithanalysisofgene expressionin hippocampal lysates from WT or Cx3cr1 -de fi cient mice (Rimmerman et al, 2017).”
de Bruin, R. G., van der Veer, E. P., Prins, J., Lee, D. H., Dane, M. J. C., Zhang, H., Roeten, M. K., Bijkerk, R., de Boer, H. C., Rabelink, T. J., et al. (2016) · Scientific Reports · doi:10.1038/srep21643 · Cited by 45 · cited 1× · see citing works
“Only genes with FDR < 0.05, fold change > 30%, and average expression > 4 TPM were included in the enrichment analysis. augmented up-regulation of Klf2 , among other genes, could mediate durable functional responses by microglia (Das et al, 2006; de Bruin et al, 2016; Roberts et al, 2017).”
InfluentialZhao, S., Li, X., Quan, J., Xi, H. S., Zhang, Y., von Schack, D., Vincent, M. S., & Zhang, B. (2016) · BMC Genomics · doi:10.1186/s12864-015-2356-9 · Cited by 41 · see citing works
Self-citationBone morphogenetic proteins in multiple sclerosis: Role in neuroinflammation
Eixarch, H., Calvo‐Barreiro, L., Montalbán, X., & Espejo, C. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.02.019 · Cited by 29 · see citing works
Xiao, F., Xu, J., & Jiang, X. (2015) · Neural Regeneration Research · doi:10.4103/1673-5374.156979 · Cited by 25 · cited 1× · see citing works
“In addition, lack of Cx3cr1 expression reduces adult neurogenesis in the HC and olfactory bulb, and impairs the integration of newborn neurons (Bachstetter et al, 2011; Rogers et al, 2011; Xiao et al, 2015; Sellner et al, 2016; Reshef et al, 2017).”
Perspectives on neuroreparative therapies for treating multiple sclerosis
Xiao, J. (2015) · Neural Regeneration Research · doi:10.4103/1673-5374.169610 · Cited by 2 · see citing works
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Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044 · see citing works
“This expression profile concurs with other studies of DAM [10,37,78,124,194].”
BackgroundResultMicroglia regulation of synaptic plasticity and learning and memory
Zhou, M., Cornell, J., Salinas, S., & Huang, H.-Y. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.322423 · Cited by 548 · see citing works
“CX3CR1/CX3CL1 signaling contributes to changes in microglia morphology and expression of immune proteins such as chemokines and chemokine receptors (Gyoneva et al., 2019).”
BackgroundMicroglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Graves, J. S., Krysko, K. M., Hua, L. H., Absinta, M., Franklin, R. J. M., & Segal, B. M. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00184-3 · Cited by 260 · see citing works
Microglia in Alzheimer’s Disease in the Context of Tau Pathology
Perea, J. R., Bolós, M., & Ávila, J. (2020) · Biomolecules · doi:10.3390/biom10101439 · Cited by 127 · see citing works
“The first one determined that Cx3cr1−/− microglia present a lower phagocytic and migratory capacity per se [242], while the second revealed that Cx3cr1−/− microglia of young animals are very similar to the wild type (WT) microglia of older animals [243].”
ResultMills, S. A., Jobling, A. I., Dixon, M., Bui, B. V., Vessey, K. A., Phipps, J. A., Greferath, U., Venables, G., Wong, V. H. Y., Wong, C. H. Y., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2112561118 · Cited by 121 · see citing works
“03), reflecting the literature showing Cx3cr1 to have a more activated inflammatory profile (29).”
BackgroundPuntambekar, S. S., Moutinho, M., Lin, P. B.-C., Jadhav, V., Tumbleson-Brink, D., Balaji, A., Benito, M. A., Xu, G., Oblak, A., Lasagna-Reeves, C. A., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00545-9 · Cited by 113 · see citing works
“Similarly, sc-RNA seq studies that have demonstrated that transcriptomic differences observed in FACS purified, CD11b+CD45+ microglia from 2 month-old B6;Cx3cr1−/− mice are not evident in aged microglia from 12 and 24 month-old Cx3cr1 deficient mice as compared to cells isolated from agematched B6;Cx3cr1+/+ animals [3…”
BackgroundMicroglial morphometric analysis: so many options, so little consistency
Reddaway, J., Richardson, P., Bevan, R. J., Stoneman, J., & Palombo, M. (2023) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2023.1211188 · Cited by 119 · see citing works
Augusto‐Oliveira, M., Arrifano, G. D. P., Delage, C. I., Tremblay, M., Lopez, M. E. C., & Verkhratsky, A. (2021) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12797 · Cited by 107 · see citing works
BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia
Sudwarts, A., Ramesha, S., Gao, T., Ponnusamy, M., Wang, S., Hansen, M. T., Kozlova, A., Bitarafan, S., Kumar, P., Beaulieu‐Abdelahad, D., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00535-x · Cited by 107 · see citing works
“A limitation of our in vivo model system relates to the inherent Cx3cr1 haploinsufficiency in Cx3cr1CreER mice which by itself is known to impact microglia via premature upregulation of an aging transcriptomic phenotype, inclusive of some disease-associated microglial genes observed in AD pathology [83].”
BackgroundWhite matter microglia heterogeneity in the CNS
Amor, S., McNamara, N. B., Gerrits, E., Marzin, M. C., Kooistra, S. M., Miron, V. E., & Nutma, E. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02389-x · Cited by 89 · see citing works
Microglia as hunters or gatherers of brain synapses
Pereira‐Iglesias, M., Maldonado-Teixidó, J., Melero, A., Piriz, J., Galea, E., Ransohoff, R. M., & Sierra, A. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01818-w · Cited by 81 · see citing works
“However, these phagocytosis-related proteins affect multiple microglial functions beyond phagocytosis, including alterations in their physiological functions, transcriptome and inflammatory responses 52–57 , and their targeted deletion does not allow discriminating between culling and scavenging.”
Self-citationBedolla, A., Wegman, E., Weed, M., Stevens, M. K., Ware, K., Paranjpe, A., Alkhimovitch, A., Ifergan, I., Таранов, А., Peter, J. D., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49596-0 · Cited by 77 · see citing works
Groh, J., Feng, R., Yuan, X., Liu, L., Klein, D., Hutahaean, G., Butz, E. S., Wang, Z., Steinbrecher, L., Neher, J. J., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01955-w · Cited by 73 · see citing works
“The rationale for using CX3CR1-deficient mice is based on the crucial role of the chemokine fractalkine (CX3CL1) and its receptor, CX3CR1, in neuroinflammation associated with neurodegenerative and demyelinating conditions 26,27 .”
Campagno, K. E., Lu, W., Jassim, A. H., Albalawi, F., Cenaj, A., Tso, H., Clark, S. P., Sripinun, P., Gómez, N. M., & Mitchell, C. H. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02251-7 · Cited by 67 · see citing works
Snijders, G. J. L., Sneeboer, M. A. M., Fernández-Andreu, A., Udine, E., (NBB-Psy), P. D. P. O. T. N. B. B., Boks, M. P., Ormel, P. R., van Berlekom, A. B., van Mierlo, H. C., Böttcher, C., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00896-z · Cited by 65 · see citing works
Nebeling, F. C., Poll, S., Justus, L. C., Mittag, M., Steffen, J., Keppler, K., & Fuhrmann, M. (2023) · eLife · doi:10.7554/elife.83176 · Cited by 64 · see citing works
Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system
Zhao, L., Hou, C., & Yan, N. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1059947 · Cited by 61 · see citing works
Harley, S. B. R., Willis, E. F., Shaikh, S., Blackmore, D. G., Sah, P., Ruitenberg, M. J., Bartlett, P. F., & Vukovic, J. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2539-20.2021 · Cited by 52 · see citing works
“(2013) demonstrated that microglia regulate synapse formation and elimination during motor learning, with microglial brain-derived neurotrophic factor (BDNF; Bennett et al., 2016; Gyoneva et al., 2019) proposed as the main molecular driver of these effects.”
BackgroundFractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease
Camacho-Hernández, N. P., & Peña‐Ortega, F. (2023) · Neural Plasticity · doi:10.1155/2023/4637073 · Cited by 51 · see citing works
“Thus, microglia synapse engulfment is deteriorated in CX3CR1-deficient mice [58], which has been linked to a higher number of dendritic spines and greater PSD95 immunoreactivity, due to a deficit in synaptic pruning in the developing hippocampus [56, 194] and which correlates with alterations in synaptic transmission…”
BackgroundTargeting innate immunity to protect and cure Alzheimer’s disease: opportunities and pitfalls
Cisbani, G., & Rivest, S. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01083-4 · Cited by 43 · see citing works
“CX3CR1 is a unique fracktalkine receptor that is expressed in microglia and circulating monocytes and it is necessary to maintain healthy homoeostatic functions of microglia [141].”
BackgroundZhao, Z., Zhang, D., Yang, F., Xu, M., Zhao, S., Pan, T., Liu, C., Liu, Y., Wu, Q., Tu, Q., et al. (2022) · Cell Research · doi:10.1038/s41422-022-00635-9 · Cited by 43 · see citing works
Microglia Drive Pockets of Neuroinflammation in Middle Age
Moca, E. N., Lecca, D., Hope, K. T., Etienne, F., Schaler, A. W., Espinoza, K., Chappell, M. S., Gray, D. T., Tweedie, D., Sidhu, S., et al. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.1922-21.2022 · Cited by 42 · see citing works
Sadeghi, I., Gispert, J. D., Palumbo, E., Muñoz-Aguirre, M., Wucher, V., D’Argenio, V., Santpere, G., Navarro, A., Guigó, R., & Vilor‐Tejedor, N. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.08.037 · Cited by 39 · see citing works
“across brain regions suggests shared perturbation of several mechanisms such as activation of microglia [77], inflammatory mechanisms, synapse development, and synaptic plasticity [54] across conditions.”
BackgroundSaitoh, B.-Y., Tanaka, E., Yamamoto, N., Kruining, D. V., Iinuma, K., Nakamuta, Y., Yamaguchi, H., Yamasaki, R., Matsumoto, K., & Kira, J.-I. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.04.008 · Cited by 47 · see citing works
Carrier, M., Šimončičová, E., St‐Pierre, M., McKee, C., & Tremblay, M. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.749737 · Cited by 37 · see citing works
Cytokine Signalling at the Microglial Penta-Partite Synapse
Aramideh, J. A., Vidal-Itriago, A., Morsch, M., & Graeber, M. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413186 · Cited by 35 · see citing works
“CXCR4/CXCR7 Human, mice microglia [67,68] Rat, mice neuron [69–73]”
BackgroundGlial cells: an important switch for the vascular function of the central nervous system
Gao, L., Pan, X., Zhang, J. H., & Xia, Y. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1166770 · Cited by 35 · see citing works
“CX3CR1 can modulate the expression of a subset of inflammatory genes to regulate the phenotype change between activated and resting microglia (Gyoneva et al., 2019).”
BackgroundAtkinson, J., Jerome, A. D., Sas, A., Munie, A. N., Wang, C., Ma, A., Arnold, W. D., & Segal, B. M. (2022) · JCI Insight · doi:10.1172/jci.insight.158153 · Cited by 35 · see citing works
“Neuronal 225 maintenance of microglial homeostasis via CX3CL1/CX3CR1 and CD200/CD200R interactions wanes 226 with aging (20-22).”
BackgroundDysfunctional microglia and tau pathology in Alzheimer’s disease
Ayyubova, G. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0087 · Cited by 35 · see citing works
Sarma, J. D., Burrows, A. C., Rayman, P. A., Hwang, M., Kundu, S., Sharma, N., Bergmann, C. C., & Sen, G. C. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1009034 · Cited by 34 · see citing works
“Despite numerous studies comparing WT, CX3CR1-/-, and CX3CR1-/+ mice, there is surprisingly little information on regulation of CX3CR1 or CX3CL1 expression at the transcriptional, translational or posttranslational levels [60].”
BackgroundMacLean, M., Juranek, J., Cuddapah, S., López-Díez, R., Ruiz, H. H., Hu, J., Frye, L., Li, H., Gugger, P. F., & Schmidt, A. M. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02191-2 · Cited by 33 · see citing works
Biological aging in multiple sclerosis
Zhang, Y., Atkinson, J., Burd, C. E., Graves, J. S., & Segal, B. M. (2023) · Multiple Sclerosis Journal · doi:10.1177/13524585231204122 · Cited by 34 · see citing works
Berki, P., Cserép, C., Környei, Z., Pósfai, B., Szabadits, E., Domonkos, A., Kellermayer, A., Nyerges, M., Wei, X., Módy, I., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49773-1 · Cited by 33 · see citing works
Microglia Susceptibility to Free Bilirubin Is Age-Dependent
Vaz, A. R., Falcão, A. S., Scarpa, E., Semproni, C., & Brites, D. M. T. O. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01012 · Cited by 26 · see citing works
“In fact, both protective and detrimental effects have been reported for CX3CR1 deletion (Gyoneva et al., 2019) and the consequences of low and high CX3CR1 expression in 2DIV and 16DIV Bf-treated microglia should be later explored in co-cultures of neurons and microglia.”
BackgroundCooper, O., Hallett, P. J., & Ole Isacson, A. (2022) · FEBS Journal · doi:10.1111/febs.16638 · Cited by 26 · see citing works
“1) [28 – 31].”
Metabolic factors in the regulation of hypothalamic innate immune responses in obesity
Folick, A., Cheang, R. T., Valdearcos, M., & Koliwad, S. K. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00666-z · Cited by 22 · see citing works
Church, K. A., Rodriguez, D., Mendiola, A. S., Vanegas, D., Gutiérrez, I. L., Tamayo, I. M., Amadu, A., Velazquez, P., Cardona, S. M., Gyoneva, S., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1130735 · Cited by 22 · see citing works
Self-citationAugusto‐Oliveira, M., Arrifano, G. D. P., Leal-Nazaré, C. G., Chaves-Filho, A. J. M., Santos-Sacramento, L., Lopes-Araújo, A., Tremblay, M., & Lopez, M. E. C. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106091 · Cited by 25 · see citing works
Zhang, W., Karschnia, P., von Mücke-Heim, I.-A., Mulazzani, M., Zhou, X., Blobner, J., Mueller, N., Teske, N., Dede, S., Xu, T., et al. (2021) · Neoplasia · doi:10.1016/j.neo.2021.09.001 · Cited by 21 · see citing works
Salcido, F. A. M., Torres-Flores, M. I., Ordaz, B., & Peña‐Ortega, F. (2022) · Glia · doi:10.1002/glia.24185 · Cited by 21 · see citing works
Injury primes mutation-bearing astrocytes for dedifferentiation in later life
Ragdale, H. S., Clements, M., Tang, W., Deltcheva, E. M., Andreassi, C., Lai, A. G., Chang, W. H., Pandrea, M., Andrew, I., Gamé, L., et al. (2023) · Current Biology · doi:10.1016/j.cub.2023.02.013 · Cited by 20 · see citing works
“A similar increase was also observed in published datasets of microglia activation following LPS treatment 36 or upon aging, 37 consistent with EGFR signaling potentially responding to neuroinflammation (Figures S3K and S3L).”
Zhou, K., Han, J., Lund, H., Boggavarapu, N. R., Lauschke, V. M., Goto, S., Cheng, H., Wang, Y., Tachi, A., Xie, C., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02381-6 · Cited by 20 · see citing works
Immune Regulation of Adult Neurogenic Niches in Health and Disease
Chintamen, S., Imessadouene, F., & Kernie, S. G. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.571071 · Cited by 20 · see citing works
“Decreased levels of CX3CR1 are associated with premature aging in microglia and result in elevated cytokines (Vukovic et al., 2012; Gyoneva et al., 2019).”
BackgroundQuickomics: exploring omics data in an intuitive, interactive and informative manner
Gao, B., Zhu, J., Negi, S., Zhang, X., Gyoneva, S., Casey, F., Wei, R., & Zhang, B. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btab255 · Cited by 17 · see citing works
Self-citationLe, L., Feidler, A. M., Rodrı́guez, L., Cealie, M. Y., Plunk, E. C., Li, H., Kara-Pabani, K., Lamantia, C. E., O’Banion, M. K., & Majewska, A. K. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.04.022 · Cited by 18 · see citing works
Sepulveda, J., Kim, J. Y., Binder, J., Vicini, S., & Rebeck, G. W. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00714-y · Cited by 19 · see citing works
“In addition, recent work [97] suggests that the loss of a single copy of CX3CR1 leads to alteration in microglial transcriptomics compared to wild-type animals.”
BackgroundDu, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00432-9 · Cited by 16 · see citing works
Schlecht, A., Thien, A., Wolf, J., Prinz, G., Agostini, H. T., Schlunck, G., Wieghofer, P., Boneva, S., & Lange, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413318 · Cited by 16 · see citing works
“Despite the fact that young mice deficient in Cx3cr1 were found to have a transcription signature that was comparable to aged mice, we used mice heterozygous for Cx3cr1 throughout our study to avoid possible effects mediated by Cx3cr1 expression differences [58].”
MethodNheu, D., Ellen, O., Ye, S., Öztürk, E., Pagnin, M., Kertadjaja, S., Theotokis, P., Grigoriadis, N., McLean, C., & Petratos, S. (2022) · Cells · doi:10.3390/cells11233768 · Cited by 16 · see citing works
Carrier, M., Hui, C. W., Watters, V., Šimončičová, E., Picard, K., Ibáñez, F. G., Vernoux, N., Droit, A., Desjardins, M., & Tremblay, M. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.11.025 · Cited by 15 · see citing works
Var, S. R., Strell, P., Johnson, S. T., Roman, A., Vasilakos, Z., & Low, W. C. (2023) · Cell Transplantation · doi:10.1177/09636897231171001 · Cited by 13 · see citing works
Cerebellar microglia: On the edge between neuroinflammation and neuroregulation
Сергеевна, Д. М., Guo, J., Shen, E.-W., Liu, W., Huang, W., Shen, Y., & Wang, L. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00550 · Cited by 13 · see citing works
“Additionally, male microglia do not exhibit the phenomenon of age-related clustering in the cerebellum observed in females (Gyoneva et al., 2019).”
Le, L., Eliseeva, S. I., Plunk, E. C., Kara-Pabani, K., Li, H., Yarovinsky, F., & Majewska, A. K. (2025) · Cell Reports · doi:10.1016/j.celrep.2024.115176 · Cited by 12 · see citing works
Respiratory syncytial virus glycoprotein G impedes CX3CR1-activation by CX3CL1 and monocyte function
Meineke, R., Agac, A., Knittler, M.-C., Ludlow, M., Osterhaus, A. D. M. E., & Rimmelzwaan, G. F. (2024) · npj Viruses · doi:10.1038/s44298-024-00075-9 · Cited by 11 · see citing works
Sirerol-Piquer, M. S., Pérez‐Villalba, A., Duart-Abadía, P., Belenguer, G., Gómez‐Pinedo, U., Blasco-Chamarro, L., Carrillo-Barberà, P., Pérez‐Cañamás, A., Navarro, V., Dehay, B., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00816-1 · Cited by 10 · see citing works
“It has been reported that Cx3cr1-deficient microglia from Cx3cr1 eGFP/eGFP young mice exhibit a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature [57].”
Stables, J., Pal, R., Bradford, B. M., Carter‐Cusack, D., Taylor, I., Pridans, C., Khan, N., Woodruff, T. M., Irvine, K. M., SUMMERS, K. M., et al. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106743 · Cited by 9 · see citing works
Targeting CX3CR1 Suppresses the Fanconi Anemia DNA Repair Pathway and Synergizes with Platinum
Lehto, J., Ninou, A. H., Chioureas, D., Jonkers, J., & Gustafsson, N. (2021) · Cancers · doi:10.3390/cancers13061442 · Cited by 7 · see citing works
“In addition, the receptor is also associated with inflammation, neurodegenerative diseases [15], and aging [16], and the CX3CR1 inhibitor KAND567 [17] is under clinical trials for hyperinflammatory conditions (EudraCT: 2020-002322-85).”
BackgroundWang, D., Hu, H., Ding, H., Zhao, H., Tian, F., & Chi, Q. (2022) · Cancer Biomarkers · doi:10.3233/cbm-210538 · Cited by 8 · see citing works
Murray, C. J., Tunderman, E. D., Vecchiarelli, H. A., Ibáñez, F. G., & Tremblay, M. (2025) · Glial health research. · doi:10.1016/j.ghres.2025.100007 · Cited by 9 · see citing works
Bui, V. T., Wu, K., Chen, C., Nguyen, A. T., Huang, W., Lee, L., Chen, W., Huang, C. F., & Shiao, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70137 · Cited by 6 · see citing works
“Deleting of CX3CR1 on microglia decreases microglial ramification and maturation in young mice [43].”
Pissarek, M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12100925 · Cited by 6 · see citing works
“Moreover, recently, CX3CR1-deficient microglia is presumed to exhibit a premature aging transcriptome and a reduced inflammatory response [89].”
BackgroundPaul, D., & Basavan, D. (2022) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-022-00446-0 · Cited by 5 · see citing works
“Similarly, absence of CX3CR1 expression will decline neurogenesis in the hippocampus and olfactory bulb of adults, and will adversely affect integration of newborn neurons [9].”
BackgroundExtracellular matrix and microglial regulation of cognitive agingPreprint
Gray, D. T., Gutierrez, A., Jami‐Alahmadi, Y., Pandey, V., Pan, L., Zhang, Y., Wohlschlegel, J. A., McDevitt, R. A., & Biase, L. M. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.04.574215 · Cited by 5 · see citing works
Augusto‐Oliveira, M., Arrifano, G. D. P., Leal-Nazaré, C. G., Soares-Silva, I., Lopes-Araújo, A., Santos-Sacramento, L., & Lopez, M. E. C. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05311-8 · Cited by 4 · see citing works
Midbrain extracellular matrix and microglia are associated with cognition in aging mice
Gray, D. T., Gutierrez, A., Jami‐Alahmadi, Y., Pandey, V., Pan, L., Zhang, Y., Wohlschlegel, J. A., McDevitt, R. A., & Biase, L. M. D. (2025) · Nature Communications · doi:10.1038/s41467-025-66434-z · Cited by 4 · see citing works
“Publicly available bulk RNA-seq datasets of isolated microglia from Cx3cr1 knockout (Cx3cr1 − / − ), Cx3Cr1 heterozygous (Cx3cr1 +/ − ), and WT micewereretrievedfromGyonevaetal.,2019 43 .”
InfluentialRNASequest: An End-to-End Reproducible RNAseq Data Analysis and Publishing Framework
Zhu, J., Sun, Y. H., Ouyang, Z., Li, K., Negi, S., Piya, S., Hu, W., Zavodszky, M. I., Yalamanchili, H. B., Chen, Y., et al. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168017 · Cited by 4 · see citing works
Self-citationConstitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia
Mroue-Ruiz, F. H., Desai, B., Garvin, M. M., Shehu, J. H., Kamau, F., Kar, U., & Bolton, J. L. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153657 · Cited by 3 · see citing works
Exploring CX3CR1 as a prognostic biomarker and immunotherapeutic target in sarcoma
Li, T., Li, X., Kang, P., & Zhao, J. (2025) · Translational Oncology · doi:10.1016/j.tranon.2025.102283 · Cited by 3 · see citing works
Lowery, R. L., Latchney, S. E., Peer, R. P., Lamantia, C. E., Opanashuk, L. A., McCall, M. N., & Majewska, A. K. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135516 · Cited by 3 · see citing works
“A moderate LPS dose has been demonstrated to induce a shift in the microglial transcriptome towards an inflammatory profile without approaching septic levels [25].”
BackgroundMethodCpeb1 remodels cell type–specific translational program to promote fear extinction
Zhang, J., Yang, C., Liu, Z., Wu, S., Li, Z.-G., Zhang, L. Y., Fan, H.-W., Guo, Z., Man, H., Li, X., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr8687 · Cited by 2 · see citing works
“Cx3cr1 is a chemokine receptor expressed on microglial cells in the brain, and disruption of Cx3cr1 is accompanied by dysfunction of microglial status and function ( 39 ).”
InfluentialRadiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration
Davids, A., Pompös, I.-M., Kociok, N., Heufelder, J., Skosyrski, S., Reichhart, N., Joussen, A. M., & Wolf, S. A. (2025) · Cells · doi:10.3390/cells14040298 · Cited by 2 · see citing works
Flow Cytometry Identification of Cell Compartments in the Murine Brain
Moffet, J. J. D., Moore, Z., Oliver, S. J., Towers, T., Jenkins, M. R., Freytag, S., Whittle, J. R., & Best, S. A. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3331-1_14 · Cited by 2 · see citing works
Microglia and border-associated macrophages in the central nervous system
Zanluqui, N. G., Polonio, C. M., de Oliveira, M. G., de Oliveira, L. G., Faria, L. C., & Peron, J. P. S. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821385-8.00013-5 · Cited by 1 · see citing works
Majewska, A. K., Le, L., Feidler, A. M., Li, H., Kara-Pabani, K., Lamantia, C. E., & O’Banion, M. K. (2024) · Research Square · doi:10.21203/rs.3.rs-3976896/v1 · Cited by 1 · see citing works
“It is worth noting that for all in vivo imaging experiments, we used mice with only one functional copy of CX3CR1, which can alter microglial transcriptomic pro�les 50 and exert a complex effect on amyloid pathology progression, slowing down disease onset but facilitating progression 51,52 .”
MethodLe, L., Eliseeva, S. I., Kara-Pabani, K., Li, H., Yarovinsky, F., & Majewska, A. K. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4795163
Microglia conduct the symphony of white matter degeneration in aging through T cell recruitment
Monteiro, J. K., & Miron, V. E. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01929-y
Ananathanarayana, V., Upadhyay, R., Illanad, G. H., Krishnan, D., Bochageri, N. P., Sevanan, M., Bagewadi, Z., Sivasamy, R., & Chinnathambi, S. (2025) · Advances in immunology · doi:10.1016/bs.ai.2025.11.002
Campagno, K. E., Lu, W., Jassim, A. H., Albalawi, F., Cenaj, A., Tso, H.-Y., Clark, S. P., Sripinun, P., Gómez, N., & Mitchell, C. H. (2021) · Figshare · doi:10.6084/m9.figshare.16650524
Du, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Figshare · doi:10.6084/m9.figshare.14059735
Campagno, K. E., Lu, W., Jassim, A. H., Albalawi, F., Cenaj, A., Tso, H.-Y., Clark, S. P., Sripinun, P., Gómez, N., & Mitchell, C. H. (2021) · Figshare · doi:10.6084/m9.figshare.16650518
Du, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Figshare · doi:10.6084/m9.figshare.14059744
Du, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Figshare · doi:10.6084/m9.figshare.14059741
Du, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Figshare · doi:10.6084/m9.figshare.14059747
Du, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Figshare · doi:10.6084/m9.figshare.14059738
Zhou, K., Han, J., Lund, H., Boggavarapu, N. R., Lauschke, V. M., Goto, S., Cheng, H., Wang, Y., Tachi, A., Xie, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18864770
Zhou, K., Han, J., Lund, H., Boggavarapu, N. R., Lauschke, V. M., Goto, S., Cheng, H., Wang, Y., Tachi, A., Xie, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18864767
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175603
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175579
Du, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Figshare · doi:10.6084/m9.figshare.14059750
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175606
Female-specific Cx3cr1-driven regulation of ALS and Alzheimer’s risk genes in tauopathy
Sudwarts, A., & Thinakaran, G. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00022-3
“Interestingly, others have reported that Cx3cr1 ablation induces an accelerated ageing, proinflammatory transcriptome [7].”
Microglia detection and phagocytosis of dying neurons is regulated by CX3CR1Preprint
Barasa, M. N., Pietramale, A. N., & Hill, R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.02.716180
“Similarly, Cx3cr1 -/- microglia have an increased pro-inflammatory signature 21,47,48 , exhibit shorter and less ramified processes 48,49 , and show increased phagocytic activity 21– 23 , all indicative of a change in microglial state.”
Djuretić, J., Ivanović, J., Jezdić, K., Todorović, V., Bufan, B., Santrač, A., & Aranđelović, J. (2026) · npj Aging · doi:10.1038/s41514-026-00364-y
Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury
Sekiguchi, K., Shoji, H., Shindo, T., Sasabe, J., Tokuyasu, D., Nakahara, J., Miyakawa, T., & Ito, D. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03848-6
“Although these molecules are involved in apoptotic cell phagocytosis [43–46], they also exert multifaceted effects on microglial physiology, transcriptomic profiles, and inflammatory responses [47–52].”
Microglial pruning of extinction-ensemble synapses preserves fear memoryPreprint
Wang, Y., Cao, Y., Liu, T., Shi, T.-T., Zhao, Y., Jin, Z., Yang, X., Wang, S. Y., Ruan, J.-Z., Zhang, F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.05.722833
Zhang, B., Zhao, R., Li, X.-Y., Wei, Z.-H., Wang, D.-M., & Lu, M.-H. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115845
Self-citationMicroglial CX3CR1 signaling mediates stress-induced pain behavior in mice
Fülöp, B., Király, Á., Petrák, R., Müller, J., Biró-Sütő, T., Kormos, V., Tékus, V., Rozmer, K., Dénes, Á., Borbély, É., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1869876
Schwab, E., Tewelde, E., Chen, L., & Benayoun, B. A. (2026) · BMC Biology · doi:10.1186/s12915-026-02672-x
Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease
Grant, R. A., Doser, R. L., & LaRocca, T. J. (2026) · Aging Cell · doi:10.1111/acel.70653
“…controls (total RNA, GSE125050 (Srinivasan et al. 2020)), Mouse Dataset 1: microglia isolated from WT mice across lifespan (total RNA, GSE131869 (Gyoneva et al. 2019)), Mouse Dataset 2: microglia isolated from rTg4510 mice (total RNA, GSE123467 (Wang et al. 2018)), Mouse Dataset 3: microglia…”
- Authors
- Gyoneva, S., Hosur, R., Gosselin, D., Zhang, B., Ouyang, Z., Cotleur, A. C., Peterson, M., Allaire, N., Challa, R., Cullen, P., Roberts, C., Miao, K., Reynolds, T. L., Glass, C. K., Burkly, L., & Ransohoff, R. M.
- Affiliations
- Biogen (United States) (US)
- University of California San Diego (US)
- Corresponding author
- Gyoneva, Stefka
- Ransohoff, Richard M
- ORCID
- Venue
- Life Science Alliance
- Publisher
- Life Science Alliance, LLC
- Published
- 2019-12
- Volume
- 2
- Issue
- 6
- Pages
- e201900453
- ISSN
- 2575-1077 (ISSN-L)
- PMC
- PMC6892408
- OpenAlex
- W2994105471
- Cited by
- 103
- References
- 68
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 23 · 2021: 25 · 2020: 7
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Life Science Alliance (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS096170)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- CX3CR1, microglia, premature aging, transcriptome, microglial aging, microglial morphology, inflammatory gene expression, active chromatin, neuroinflammation
- MeSH terms
- CX3C Chemokine Receptor 1, Genetic Profile, Animals, Disease Models, Animal, Female, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Signal Transduction, Gene Deletion, Microglia, Mice, Knockout, Aging, Premature, Receptors, Chemokine, Mice, Transcriptome
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