{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:24:27Z","timestamp":1792790667210,"version":"4.5.0"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":62,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008483","name":"NOMIS Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000854","name":"Human Frontier Science Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CJD Foundation GELU Foundation","id":[{"id":"https:\/\/ror.org\/01j5a9j34","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Candoc UZH fellowship CJD foundation","id":[{"id":"https:\/\/ror.org\/05d2ptg05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurodegenerative disorders display brain region tropism accompanied by the emergence of distinct cellular states that contribute to disease pathogenesis, with molecular alterations occurring predominantly in glial cells. Here we show the emergence of a microglial state with distinct spatial distribution in the brains of terminally sick prion-infected mice characterized by high expression of Gpnmb (glycoprotein non-metastatic melanoma protein B), transcriptional signatures consistent with phagocytic activity, and increased expression of lysosomal genes in regions undergoing pronounced cell death. We find that this cellular state is not induced by pathological protein aggregates but by soluble factors released by dying cells regardless of the initiating insult. This work defines Gpnmb\u207a microglia as a\u00a0distinct phagocytic state that links cell death to microglial activation and reveals a generalizable mechanism by which microglia respond to cell loss.<\/jats:p>","DOI":"10.1038\/s41467-026-73003-5","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T03:16:10Z","timestamp":1778555770000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gpnmb defines a phagocytic state of microglia linked to cell death in prion disease mouse model"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-894X","authenticated-orcid":false,"given":"Davide","family":"Caredio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Mariutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5279-0883","authenticated-orcid":false,"given":"Lisa","family":"Polzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Gatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Cerisoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Laimeche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Miracca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Droux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-5283","authenticated-orcid":false,"given":"Mohamad","family":"El Amki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Emmenegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9253-4362","authenticated-orcid":false,"given":"Marian","family":"Hruska-Plochan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4369-7023","authenticated-orcid":false,"given":"Susanne","family":"Wegener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1271-9445","authenticated-orcid":false,"given":"Magdalini","family":"Polymenidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-2596","authenticated-orcid":false,"given":"Elena","family":"De Cecco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-6708","authenticated-orcid":false,"given":"Adriano","family":"Aguzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"73003_CR1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1111\/j.1750-3639.1995.tb00625.x","volume":"5","author":"H Budka","year":"1995","unstructured":"Budka, H. et al. Neuropathological diagnostic criteria for creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (Prion Diseases). Brain Pathol. 5, 459\u2013466 (1995).","journal-title":"Brain Pathol."},{"key":"73003_CR2","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1002\/ana.410340617","volume":"34","author":"I Ferrer","year":"1993","unstructured":"Ferrer, I., Casas, R. & Rivera, R. Parvalbumin-immunoreactive cortical neurons in Creutzfeldt-Jakob disease. Ann. Neurol. 34, 864\u2013866 (1993).","journal-title":"Ann. Neurol."},{"key":"73003_CR3","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1750-3639.1998.tb00188.x","volume":"8","author":"M Guentchev","year":"1998","unstructured":"Guentchev, M., Groschup, M. H., Kordek, R., Liberski, P. P. & Budka, H. Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies. Brain Pathol. 8, 615\u2013623 (1998).","journal-title":"Brain Pathol."},{"key":"73003_CR4","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0002-9440(10)65459-4","volume":"155","author":"M Guentchev","year":"1999","unstructured":"Guentchev, M., Wanschitz, J., Voigtlander, T., Flicker, H. & Budka, H. Selective neuronal vulnerability in human prion diseases. Fatal familial insomnia differs from other types of prion diseases. Am. J. Pathol. 155, 1453\u20131457 (1999).","journal-title":"Am. J. Pathol."},{"key":"73003_CR5","doi-asserted-by":"publisher","unstructured":"Scheckel, C., Imeri, M., Schwarz, P. & Aguzzi, A. Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons. Elife. 9, https:\/\/doi.org\/10.7554\/elife.62911 (2020).","DOI":"10.7554\/elife.62911"},{"key":"73003_CR6","doi-asserted-by":"publisher","first-page":"e1008653","DOI":"10.1371\/journal.ppat.1008653","volume":"16","author":"S Sorce","year":"2020","unstructured":"Sorce, S. et al. Genome-wide transcriptomics identifies an early preclinical signature of prion infection. PLoS Pathog. 16, e1008653 (2020).","journal-title":"PLoS Pathog."},{"key":"73003_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0306-4522(96)00212-6","volume":"74","author":"S Betmouni","year":"1996","unstructured":"Betmouni, S., Perry, V. H. & Gordon, J. L. Evidence for an early inflammatory response in the central nervous system of mice with scrapie. Neuroscience 74, 1\u20135 (1996).","journal-title":"Neuroscience"},{"key":"73003_CR8","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1006\/exnr.1997.6424","volume":"144","author":"A Williams","year":"1997","unstructured":"Williams, A., Lucassen, P. J., Ritchie, D. & Bruce, M. PrP Deposition, Microglial Activation, and Neuronal Apoptosis in Murine Scrapie. Exp. Neurol. 144, 433\u2013438 (1997).","journal-title":"Exp. Neurol."},{"key":"73003_CR9","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1111\/j.1750-3639.1998.tb00167.x","volume":"8","author":"A Giese","year":"1998","unstructured":"Giese, A. et al. Role of microglia in neuronal cell death in prion disease. Brain Pathol. 8, 449\u2013457 (1998).","journal-title":"Brain Pathol."},{"key":"73003_CR10","doi-asserted-by":"crossref","unstructured":"Liu, Y. et al. NG2 glia protect against prion neurotoxicity by inhibiting microglia-to-neuron prostaglandin E2 signaling. Nat. Neurosci. 27, 1534\u20131544","DOI":"10.1038\/s41593-024-01663-x"},{"key":"73003_CR11","doi-asserted-by":"publisher","first-page":"e1012552","DOI":"10.1371\/journal.ppat.1012552","volume":"20","author":"D Caredio","year":"2024","unstructured":"Caredio, D. et al. Prion diseases disrupt glutamate\/glutamine metabolism in skeletal muscle. PLOS Pathog. 20, e1012552 (2024).","journal-title":"PLOS Pathog."},{"key":"73003_CR12","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1126\/science.1110647","volume":"308","author":"A Nimmerjahn","year":"2005","unstructured":"Nimmerjahn, A., Kirchhoff, F. & Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314\u20131318 (2005).","journal-title":"Science"},{"key":"73003_CR13","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/BF00334672","volume":"85","author":"M Barcikowska","year":"1993","unstructured":"Barcikowska, M. et al. Microglia is a component of the prion protein amyloid plaque in the Gerstmann-Str\u00e4ussler-Scheinker syndrome. Acta Neuropathol. 85, 623\u2013627 (1993).","journal-title":"Acta Neuropathol."},{"key":"73003_CR14","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1007\/BF00294180","volume":"87","author":"DC Guiroy","year":"1994","unstructured":"Guiroy, D. C., Wakayama, I., Liberski, P. P. & Gajdusek, D. C. Relationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Gerstmann-Str\u00e4ussler syndrome. Acta Neuropathol. 87, 526\u2013530 (1994).","journal-title":"Acta Neuropathol."},{"key":"73003_CR15","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/BF00369445","volume":"86","author":"A Sasaki","year":"1993","unstructured":"Sasaki, A., Hirato, J. & Nakazato, Y. Immunohistochemical study of microglia in the Creutzfeldt-Jakob diseased brain. Acta Neuropathol. 86, 337\u2013344 (1993).","journal-title":"Acta Neuropathol."},{"key":"73003_CR16","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1365-2990.1994.tb00956.x","volume":"20","author":"AE Williams","year":"1994","unstructured":"Williams, A. E., Lawson, L. J., Perry, V. H. & Fraser, H. Characterization of the microglial response in murine scrapie. Neuropathol. Appl Neurobiol. 20, 47\u201355 (1994).","journal-title":"Neuropathol. Appl Neurobiol."},{"key":"73003_CR17","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nn2028","volume":"11","author":"J Falsig","year":"2008","unstructured":"Falsig, J. et al. A versatile prion replication assay in organotypic brain slices. Nat. Neurosci. 11, 109\u2013117 (2008).","journal-title":"Nat. Neurosci."},{"key":"73003_CR18","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1084\/jem.20151000","volume":"213","author":"C Zhu","year":"2016","unstructured":"Zhu, C. et al. A neuroprotective role for microglia in prion diseases. J. Exp. Med 213, 1047\u20131059 (2016).","journal-title":"J. Exp. Med"},{"key":"73003_CR19","doi-asserted-by":"publisher","unstructured":"Carroll, J. A., Race, B., Williams, K., Striebel, J. & Chesebro, B. Microglia are critical in host defense against prion disease. J. Virol. 92, https:\/\/doi.org\/10.1128\/JVI.00549-18 (2018).","DOI":"10.1128\/JVI.00549-18"},{"key":"73003_CR20","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1002\/glia.24244","volume":"70","author":"BM Bradford","year":"2022","unstructured":"Bradford, B. M., McGuire, L. I., Hume, D. A., Pridans, C. & Mabbott, N. A. Microglia deficiency accelerates prion disease but does not enhance prion accumulation in the brain. Glia 70, 2169\u20132187 (2022).","journal-title":"Glia"},{"key":"73003_CR21","doi-asserted-by":"publisher","first-page":"eaba3239","DOI":"10.1126\/sciadv.aba3239","volume":"6","author":"EC Damisah","year":"2020","unstructured":"Damisah, E. C. et al. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Sci. Adv. 6, eaba3239 (2020).","journal-title":"Sci. Adv."},{"key":"73003_CR22","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.3390\/ijms22042196","volume":"22","author":"B Li","year":"2021","unstructured":"Li, B., Chen, M. & Zhu, C. Neuroinflammation in Prion Disease. Int. J. Mol. Sci. 22, 2196 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"73003_CR23","doi-asserted-by":"publisher","first-page":"10905","DOI":"10.1128\/JVI.76.21.10905-10913.2002","volume":"76","author":"CA Baker","year":"2002","unstructured":"Baker, C. A., Martin, D. & Manuelidis, L. Microglia from Creutzfeldt-Jakob disease-infected brains are infectious and show specific mRNA activation profiles. J. Virol. 76, 10905\u201310913 (2002).","journal-title":"J. Virol."},{"key":"73003_CR24","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1126\/science.1227901","volume":"339","author":"A Aguzzi","year":"2013","unstructured":"Aguzzi, A., Barres, B. A. & Bennett, M. L. Microglia: scapegoat, saboteur, or something else?. Science 339, 156\u2013161 (2013).","journal-title":"Science"},{"key":"73003_CR25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s40478-022-01450-4","volume":"10","author":"JA Slota","year":"2022","unstructured":"Slota, J. A., Sajesh, B. V., Frost, K. F., Medina, S. J. & Booth, S. A. Dysregulation of neuroprotective astrocytes, a spectrum of microglial activation states, and altered hippocampal neurogenesis are revealed by single-cell RNA sequencing in prion disease. Acta Neuropathol. Commun. 10, 161 (2022).","journal-title":"Acta Neuropathol. Commun."},{"key":"73003_CR26","doi-asserted-by":"publisher","unstructured":"Dimitriadis, A. et al. Single-nuclei transcriptomics of mammalian prion diseases identifies dynamic gene signatures shared between species. Preprint at https:\/\/doi.org\/10.1101\/2022.09.13.507650 (2022).","DOI":"10.1101\/2022.09.13.507650"},{"key":"73003_CR27","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s40478-018-0612-3","volume":"6","author":"M H\u00fcttenrauch","year":"2018","unstructured":"H\u00fcttenrauch, M. et al. Glycoprotein NMB: a novel Alzheimer's disease associated marker expressed in a subset of activated microglia. Acta Neuropathol. Commun. 6, 108 (2018).","journal-title":"Acta Neuropathol. Commun."},{"key":"73003_CR28","doi-asserted-by":"publisher","unstructured":"van der Vliet, D. et al. Foamy microglia link oxylipins to disease progression in multiple sclerosis. Preprint at https:\/\/doi.org\/10.1101\/2024.10.18.619040 (2024).","DOI":"10.1101\/2024.10.18.619040"},{"key":"73003_CR29","doi-asserted-by":"crossref","unstructured":"Wallings, R. L. et al. ASO-mediated knock-down of GPNMB in mutant-GRN and in Grn-deficient peripheral myeloid cells disrupts lysosomal function and immune responses. Mol. Neurodegeneration 20, 41 (2025).","DOI":"10.1186\/s13024-025-00829-w"},{"key":"73003_CR30","doi-asserted-by":"crossref","unstructured":"Xiang, R. et al. Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution. Neuron 113, 2102\u20132122 (2024).","DOI":"10.1016\/j.neuron.2025.04.026"},{"key":"73003_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30033-z","volume":"13","author":"BF Miller","year":"2022","unstructured":"Miller, B. F., Huang, F., Atta, L., Sahoo, A. & Fan, J. Reference-free cell type deconvolution of multi-cellular pixel-resolution spatially resolved transcriptomics data. Nat. Commun. 13, 2339 (2022).","journal-title":"Nat. Commun."},{"key":"73003_CR32","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.3174\/ajnr.A0496","volume":"28","author":"HJ Tschampa","year":"2007","unstructured":"Tschampa, H. J. et al. Pattern of cortical changes in sporadic Creutzfeldt-Jakob disease. AJNR Am. J. Neuroradiol. 28, 1114\u20131118 (2007).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"73003_CR33","doi-asserted-by":"publisher","first-page":"19727","DOI":"10.1073\/pnas.1803521116","volume":"116","author":"E Kanata","year":"2019","unstructured":"Kanata, E. et al. RNA editing alterations define manifestation of prion diseases. Proc. Natl. Acad. Sci. USA 116, 19727\u201319735 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73003_CR34","doi-asserted-by":"publisher","first-page":"e0120194","DOI":"10.1371\/journal.pone.0120194","volume":"10","author":"H Zigdon","year":"2015","unstructured":"Zigdon, H. et al. Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease. PLOS ONE 10, e0120194 (2015).","journal-title":"PLOS ONE"},{"key":"73003_CR35","doi-asserted-by":"crossref","unstructured":"Zhu, X.-C. et al. CSF GPNMB in Parkinson's disease: A potential association with age and microglial activation. J. Parkinson\u2019s Dis.14, 1533\u20131542 (2024).","DOI":"10.1177\/1877718X241288712"},{"key":"73003_CR36","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13195-021-00828-1","volume":"13","author":"F Aichholzer","year":"2021","unstructured":"Aichholzer, F. et al. Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer's disease. Alzheimers Res. Ther. 13, 94 (2021).","journal-title":"Alzheimers Res. Ther."},{"key":"73003_CR37","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s12031-019-01411-y","volume":"69","author":"S Zhu","year":"2019","unstructured":"Zhu, S. et al. Targeted multiple reaction monitoring analysis of CSF identifies UCHL1 and GPNMB as candidate biomarkers for ALS. J. Mol. Neurosci. 69, 643\u2013657 (2019).","journal-title":"J. Mol. Neurosci."},{"key":"73003_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/srep16920","volume":"5","author":"A Katayama","year":"2015","unstructured":"Katayama, A. et al. Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis. Sci. Rep. 5, 16920 (2015).","journal-title":"Sci. Rep."},{"key":"73003_CR39","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.bcmd.2016.12.002","volume":"68","author":"V Murugesan","year":"2018","unstructured":"Murugesan, V. et al. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease. Blood Cells, Mol. Dis. 68, 47\u201353 (2018).","journal-title":"Blood Cells, Mol. Dis."},{"key":"73003_CR40","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/ki.2012.218","volume":"82","author":"BR Conway","year":"2012","unstructured":"Conway, B. R. et al. Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors. Kidney Int. 82, 812\u2013818 (2012).","journal-title":"Kidney Int."},{"key":"73003_CR41","doi-asserted-by":"publisher","first-page":"e36574","DOI":"10.1016\/j.heliyon.2024.e36574","volume":"10","author":"Y-Y Liu","year":"2024","unstructured":"Liu, Y.-Y. et al. Biofluid GPNMB\/osteoactivin as a potential biomarker of ageing: A cross-sectional study. Heliyon 10, e36574 (2024).","journal-title":"Heliyon"},{"key":"73003_CR42","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13195-021-00828-1","volume":"13","author":"F Aichholzer","year":"2021","unstructured":"Aichholzer, F. et al. Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer\u2019s disease. Alzheimer's. Res. Ther. 13, 94 (2021).","journal-title":"Alzheimer's. Res. Ther."},{"key":"73003_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02965-w","volume":"20","author":"DA Gillett","year":"2023","unstructured":"Gillett, D. A., Wallings, R. L., Uriarte Huarte, O. & Tansey, M. G. Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease. J. Neuroinflammation 20, 286 (2023).","journal-title":"J. Neuroinflammation"},{"key":"73003_CR44","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/jcm12144689","volume":"12","author":"J Doroszkiewicz","year":"2023","unstructured":"Doroszkiewicz, J. et al. Potential utility of cerebrospinal fluid glycoprotein nonmetastatic melanoma protein B as a neuroinflammatory diagnostic biomarker in mild cognitive impairment and alzheimer's disease. J. Clin. Med. 12, 14 (2023).","journal-title":"J. Clin. Med."},{"key":"73003_CR45","doi-asserted-by":"publisher","unstructured":"Erdenebat, T. et al. Excitatory neuron-prone prion propagation and excitatory neuronal loss in prion-infected mice. Front. Mol. Neurosci. https:\/\/doi.org\/10.3389\/fnmol.2024.1498142 (2024).","DOI":"10.3389\/fnmol.2024.1498142"},{"key":"73003_CR46","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","volume":"47","author":"S Krasemann","year":"2017","unstructured":"Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566\u2013581 (2017).","journal-title":"Immunity"},{"key":"73003_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-86991-z","volume":"15","author":"F Ouyang","year":"2025","unstructured":"Ouyang, F. et al. Glycosylated lysosomal membrane protein promotes tissue repair after spinal cord injury by reducing iron deposition and ferroptosis in microglia. Sci. Rep. 15, 2867 (2025).","journal-title":"Sci. Rep."},{"key":"73003_CR48","unstructured":"Alvarez-Valadez, K. et al. Methods in Cell Biology. (Academic Press, 2021)."},{"key":"73003_CR49","doi-asserted-by":"crossref","unstructured":"Chou, C.-C. et al. Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer\u2019s disease. Nat. Cell Biol.27, 619\u2013632 (2025).","DOI":"10.1038\/s41556-025-01623-y"},{"key":"73003_CR50","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.devcel.2019.10.025","volume":"52","author":"J Jia","year":"2020","unstructured":"Jia, J. et al. Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal. Dev. Cell 52, 69\u201387 (2020).","journal-title":"Dev. Cell"},{"key":"73003_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/srep10062","volume":"5","author":"A Wenborn","year":"2015","unstructured":"Wenborn, A. et al. A novel and rapid method for obtaining high titre intact prion strains from mammalian brain. Sci. Rep. 5, 10062 (2015).","journal-title":"Sci. Rep."},{"key":"73003_CR52","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41586-024-07042-7","volume":"626","author":"M Hruska-Plochan","year":"2024","unstructured":"Hruska-Plochan, M. et al. A model of human neural networks reveals NPTX2 pathology in ALS and FTLD. Nature 626, 1073\u20131083 (2024).","journal-title":"Nature"},{"key":"73003_CR53","doi-asserted-by":"publisher","first-page":"e71098","DOI":"10.1371\/journal.pone.0071098","volume":"8","author":"B van Wilgenburg","year":"2013","unstructured":"van Wilgenburg, B., Browne, C., Vowles, J. & Cowley, S. A. Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions. PLoS ONE 8, e71098 (2013).","journal-title":"PLoS ONE"},{"key":"73003_CR54","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13287-019-1163-7","volume":"10","author":"D Bohaciakova","year":"2019","unstructured":"Bohaciakova, D. et al. A scalable solution for isolating human multipotent clinical-grade neural stem cells from ES precursors. Stem Cell Res. Ther. 10, 83 (2019).","journal-title":"Stem Cell Res. Ther."},{"key":"73003_CR55","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s12015-016-9670-8","volume":"12","author":"AM Ansari","year":"2016","unstructured":"Ansari, A. M. et al. Cellular GFP toxicity and immunogenicity: potential confounders in in vivo cell tracking experiments. Stem Cell Rev. Rep. 12, 553\u2013559 (2016).","journal-title":"Stem Cell Rev. Rep."},{"key":"73003_CR56","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1006\/bbrc.1999.0954","volume":"260","author":"H-S Liu","year":"1999","unstructured":"Liu, H.-S., Jan, M.-S., Chou, C.-K., Chen, P.-H. & Ke, N.-J. Is green fluorescent protein toxic to the living cells?. Biochem. Biophys. Res. Commun. 260, 712\u2013717 (1999).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"73003_CR57","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul, H. et al. A unique microglia typeassociated with restricting development of Alzheimer's disease. Cell 169, 1276\u20131290 (2017).","journal-title":"Cell"},{"key":"73003_CR58","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.nbd.2008.10.006","volume":"33","author":"R Kimura","year":"2009","unstructured":"Kimura, R. & Ohno, M. Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model. Neurobiol. Dis. 33, 229\u2013235 (2009).","journal-title":"Neurobiol. Dis."},{"key":"73003_CR59","doi-asserted-by":"publisher","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","volume":"26","author":"H Oakley","year":"2006","unstructured":"Oakley, H. et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J. Neurosci. 26, 10129\u201310140 (2006).","journal-title":"J. Neurosci."},{"key":"73003_CR60","doi-asserted-by":"publisher","first-page":"eadg1323","DOI":"10.1126\/scitranslmed.adg1323","volume":"16","author":"B Han","year":"2024","unstructured":"Han, B. et al. Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain. Sci. Transl. Med. 16, eadg1323 (2024).","journal-title":"Sci. Transl. Med."},{"key":"73003_CR61","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.nbd.2009.11.018","volume":"37","author":"AL De Lella Ezcurra","year":"2010","unstructured":"De Lella Ezcurra, A. L., Chertoff, M., Ferrari, C., Graciarena, M. & Pitossi, F. Chronic expression of low levels of tumor necrosis factor-alpha in the substantia nigra elicits progressive neurodegeneration, delayed motor symptoms and microglia\/macrophage activation. Neurobiol. Dis. 37, 630\u2013640 (2010).","journal-title":"Neurobiol. Dis."},{"key":"73003_CR62","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1111\/j.1471-4159.2004.02399.x","volume":"89","author":"B Ferger","year":"2004","unstructured":"Ferger, B., Leng, A., Mura, A., Hengerer, B. & Feldon, J. Genetic ablation of tumor necrosis factor-alpha (TNF-alpha) and pharmacological inhibition of TNF-synthesis attenuates MPTP toxicity in mouse striatum. J. Neurochem. 89, 822\u2013833 (2004).","journal-title":"J. Neurochem."},{"key":"73003_CR63","doi-asserted-by":"publisher","first-page":"21","DOI":"10.2174\/156720510790274428","volume":"7","author":"C Zhang","year":"2010","unstructured":"Zhang, C., Browne, A., Kim, D. Y. & Tanzi, R. E. Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage. Curr. Alzheimer Res. 7, 21\u201326 (2010).","journal-title":"Curr. Alzheimer Res."},{"key":"73003_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-8-27","volume":"8","author":"EL Tobinick","year":"2008","unstructured":"Tobinick, E. L. & Gross, H. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease. BMC Neurol. 8, 27 (2008).","journal-title":"BMC Neurol."},{"key":"73003_CR65","doi-asserted-by":"crossref","unstructured":"Limone, F. et al. Single-nucleus sequencing reveals enriched expression of genetic risk factors in Extratelencephalic Neurons sensitive to degeneration in ALS. Nat. Aging 4, 984\u2013997 (2023).","DOI":"10.1038\/s43587-024-00640-0"},{"key":"73003_CR66","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S0167-0115(02)00288-4","volume":"111","author":"PS Bandari","year":"2003","unstructured":"Bandari, P. S. et al. Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P. Regul. Pept. 111, 169\u2013178 (2003).","journal-title":"Regul. Pept."},{"key":"73003_CR67","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3390\/ijms20010066","volume":"20","author":"MJC Van der Lienden","year":"2019","unstructured":"Van der Lienden, M. J. C., Gaspar, P., Boot, R., Aerts, J. M. F. G. & Van Eijk, M. Glycoprotein non-metastatic protein B: an emerging biomarker for lysosomal dysfunction in macrophages. Int. J. Mol. Sci. 20, 66 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"73003_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-00196-0","volume":"9","author":"Q Song","year":"2020","unstructured":"Song, Q., Meng, B., Xu, H. & Mao, Z. The emerging roles of vacuolar-type ATPase-dependent Lysosomal acidification in neurodegenerative diseases. Transl. Neurodegen. 9, 17 (2020).","journal-title":"Transl. Neurodegen."},{"key":"73003_CR69","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1111\/ejn.12169","volume":"37","author":"DM Wolfe","year":"2013","unstructured":"Wolfe, D. M. et al. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. Eur. J. Neurosci. 37, 1949\u20131961 (2013).","journal-title":"Eur. J. Neurosci."},{"key":"73003_CR70","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1074\/jbc.M112.409250","volume":"288","author":"L Avrahami","year":"2013","unstructured":"Avrahami, L. et al. Inhibition of glycogen synthase kinase-3 ameliorates \u03b2-amyloid pathology and restores lysosomal acidification and mammalian target of rapamycin activity in the Alzheimer disease mouse model: in vivo and in vitro studies. J. Biol. Chem. 288, 1295\u20131306 (2013).","journal-title":"J. Biol. Chem."},{"key":"73003_CR71","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/ng1884","volume":"38","author":"A Ramirez","year":"2006","unstructured":"Ramirez, A. et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat. Genet. 38, 1184\u20131191 (2006).","journal-title":"Nat. Genet."},{"key":"73003_CR72","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1093\/hmg\/ddt180","volume":"22","author":"O Korvatska","year":"2013","unstructured":"Korvatska, O. et al. Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). Hum. Mol. Genet. 22, 3259\u20133268 (2013).","journal-title":"Hum. Mol. Genet."},{"key":"73003_CR73","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41593-023-01494-2","volume":"27","author":"B Wang","year":"2024","unstructured":"Wang, B. et al. TFEB\u2013vacuolar ATPase signaling regulates lysosomal function and microglial activation in tauopathy. Nat. Neurosci. 27, 48\u201362 (2024).","journal-title":"Nat. Neurosci."},{"key":"73003_CR74","doi-asserted-by":"publisher","first-page":"6736","DOI":"10.1093\/hmg\/ddv380","volume":"24","author":"A Dubos","year":"2015","unstructured":"Dubos, A. et al. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration. Hum. Mol. Genet. 24, 6736\u20136755 (2015).","journal-title":"Hum. Mol. Genet."},{"key":"73003_CR75","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.cell.2008.04.037","volume":"133","author":"F Peri","year":"2008","unstructured":"Peri, F. & N\u00fcsslein-Volhard, C. Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133, 916\u2013927 (2008).","journal-title":"Cell"},{"key":"73003_CR76","doi-asserted-by":"publisher","first-page":"46396","DOI":"10.1074\/jbc.M303924200","volume":"278","author":"T Nishi","year":"2003","unstructured":"Nishi, T., Kawasaki-Nishi, S. & Forgac, M. Expression and function of the mouse V-ATPase d subunit isoforms. J. Biol. Chem. 278, 46396\u201346402 (2003).","journal-title":"J. Biol. Chem."},{"key":"73003_CR77","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-10522-3","volume":"12","author":"M Suda","year":"2022","unstructured":"Suda, M. et al. Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells. Sci. Rep. 12, 6522 (2022).","journal-title":"Sci. Rep."},{"key":"73003_CR78","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","volume":"101","author":"Q Li","year":"2019","unstructured":"Li, Q. et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron 101, 207\u2013223 (2019).","journal-title":"Neuron"},{"key":"73003_CR79","doi-asserted-by":"crossref","unstructured":"Zhu, K. et al. TGF\u03b2 signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration. Nat. Neurosci. 29, 617\u2013631 (2026).","DOI":"10.1038\/s41593-025-02161-4"},{"key":"73003_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39447-9","volume":"14","author":"P Androvic","year":"2023","unstructured":"Androvic, P. et al. Spatial transcriptomics-correlated electron microscopy maps transcriptional and ultrastructural responses to brain injury. Nat. Commun. 14, 4115 (2023).","journal-title":"Nat. Commun."},{"key":"73003_CR81","doi-asserted-by":"publisher","first-page":"809806","DOI":"10.3389\/fimmu.2021.809806","volume":"12","author":"J Zhao","year":"2021","unstructured":"Zhao, J., Jiang, P., Guo, S., Schrodi, S. J. & He, D. Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in rheumatoid arthritis. Front. Immunol. 12, 809806 (2021).","journal-title":"Front. Immunol."},{"key":"73003_CR82","first-page":"4767","volume":"24","author":"B Li","year":"2010","unstructured":"Li, B. et al. The melanoma-associated transmembrane glycoprotein Gpnmb controls trafficking of cellular debris for degradation and is essential for tissue repair. Faseb J. 24, 4767\u20134781 (2010).","journal-title":"Faseb J."},{"key":"73003_CR83","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41586-020-2709-7","volume":"588","author":"J Zhang","year":"2020","unstructured":"Zhang, J. et al. Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency. Nature 588, 459\u2013465 (2020).","journal-title":"Nature"},{"key":"73003_CR84","doi-asserted-by":"publisher","first-page":"115343","DOI":"10.1016\/j.celrep.2025.115343","volume":"44","author":"M Liu","year":"2025","unstructured":"Liu, M. et al. GPNMB and ATP6V1A interact to mediate microglia phagocytosis of multiple types of pathological particles. Cell Rep. 44, 115343 (2025).","journal-title":"Cell Rep."},{"key":"73003_CR85","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1038\/s41590-023-01558-2","volume":"24","author":"MJ Dolan","year":"2023","unstructured":"Dolan, M. J. et al. Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro. Nat. Immunol. 24, 1382\u20131390 (2023).","journal-title":"Nat. Immunol."},{"key":"73003_CR86","doi-asserted-by":"publisher","unstructured":"McFarland, K. N. et al. Microglia show differential transcriptomic response to A\u03b2 peptide aggregates ex vivo and in vivo. Life Sci. Alliance. https:\/\/doi.org\/10.26508\/lsa.202101108 (2021).","DOI":"10.26508\/lsa.202101108"},{"key":"73003_CR87","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15778-8","volume":"7","author":"S Vanni","year":"2017","unstructured":"Vanni, S. et al. Differential overexpression of SERPINA3 in human prion diseases. Sci. Rep. 7, 15637 (2017).","journal-title":"Sci. Rep."},{"key":"73003_CR88","doi-asserted-by":"publisher","first-page":"3778","DOI":"10.1007\/s12035-022-02817-3","volume":"59","author":"M Zattoni","year":"2022","unstructured":"Zattoni, M. et al. Serpin signatures in prion and alzheimer\u2019s diseases. Mol. Neurobiol. 59, 3778\u20133799 (2022).","journal-title":"Mol. Neurobiol."},{"key":"73003_CR89","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.expneurol.2012.08.005","volume":"238","author":"M El Amki","year":"2012","unstructured":"El Amki, M. et al. Experimental modeling of recombinant tissue plasminogen activator effects after ischemic stroke. Exp. Neurol. 238, 138\u2013144 (2012).","journal-title":"Exp. Neurol."},{"key":"73003_CR90","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1161\/STROKEAHA.107.487520","volume":"38","author":"C Orset","year":"2007","unstructured":"Orset, C. et al. Mouse model of in situ thromboembolic stroke and reperfusion. Stroke 38, 2771\u20132778 (2007).","journal-title":"Stroke"},{"key":"73003_CR91","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1038\/s41596-020-00472-3","volume":"16","author":"A Nott","year":"2021","unstructured":"Nott, A., Schlachetzki, J. C. M., Fixsen, B. R. & Glass, C. K. Nuclei isolation of multiple brain cell types for omics interrogation. Nat. Protoc. 16, 1629\u20131646 (2021).","journal-title":"Nat. Protoc."},{"key":"73003_CR92","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","volume":"8","author":"SL Wolock","year":"2019","unstructured":"Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281\u2013291 (2019).","journal-title":"Cell Syst."},{"key":"73003_CR93","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-1950-6","volume":"21","author":"S Yang","year":"2020","unstructured":"Yang, S. et al. Decontamination of ambient RNA in single-cell RNA-seq with DecontX. Genome Biol. 21, 57 (2020).","journal-title":"Genome Biol."},{"key":"73003_CR94","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902 (2019).","journal-title":"Cell"},{"key":"73003_CR95","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"73003_CR96","doi-asserted-by":"publisher","first-page":"e202000814","DOI":"10.26508\/lsa.202000814","volume":"3","author":"M Avar","year":"2020","unstructured":"Avar, M. et al. Prion infection, transmission, and cytopathology modeled in a low-biohazard human cell line. Life Sci. Alliance 3, e202000814 (2020).","journal-title":"Life Sci. Alliance"},{"key":"73003_CR97","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41551-024-01278-4","volume":"9","author":"J-A Yin","year":"2025","unstructured":"Yin, J.-A. et al. Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes. Nat. Biomed. Eng. 9, 127\u2013148 (2025).","journal-title":"Nat. Biomed. Eng."},{"key":"73003_CR98","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"73003_CR99","doi-asserted-by":"crossref","unstructured":"Phan, T. K., Poon, I. K. & Atkin-Smith, G. K. Detection and isolation of apoptotic bodies to high purity. J. Vis. Exp. 138, 58317 (2018).","DOI":"10.3791\/58317"},{"key":"73003_CR100","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/978-1-60761-744-0_2","volume":"670","author":"WB Stine","year":"2011","unstructured":"Stine, W. B., Jungbauer, L., Yu, C. & LaDu, M. J. Preparing synthetic A\u03b2 in different aggregation states. Methods Mol. Biol. 670, 13\u201332 (2011).","journal-title":"Methods Mol. Biol."},{"key":"73003_CR101","doi-asserted-by":"publisher","first-page":"e3872","DOI":"10.1371\/journal.pone.0003872","volume":"3","author":"M Polymenidou","year":"2008","unstructured":"Polymenidou, M. et al. The POM monoclonals: a comprehensive set of antibodies to non-overlapping prion protein epitopes. PLoS ONE 3, e3872 (2008).","journal-title":"PLoS ONE"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73003-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73003-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73003-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:01:56Z","timestamp":1783954916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73003-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["73003"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-73003-5","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"19 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6138"}}