{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:42:32Z","timestamp":1790703752648,"version":"4.1.0"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"8","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1801681"],"award-info":[{"award-number":["U1801681"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,2,21]]},"abstract":"<jats:p>\n                    Microglia play a critical role in the pathogenic process of neurodegenerative diseases, such as Parkinson\u2019s disease (PD) and Alzheimer\u2019s disease (AD). Upon pathological stimulation, microglia are converted from a surveillant to an overactivated phenotype. However, the molecular characters of proliferating microglia and their contributions to the pathogenesis of neurodegeneration remain unclear. Here, we identify chondroitin sulfate proteoglycan 4 (\n                    <jats:italic>Cspg4,<\/jats:italic>\n                    also known as neural\/glial antigen 2)-expressing microglia as a specific subset of microglia with proliferative capability during neurodegeneration. We found that the percentage of\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    microglia was increased in mouse models of PD. The transcriptomic analysis of\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    microglia revealed that the subcluster\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>high<\/jats:sup>\n                    <\/jats:italic>\n                    microglia displayed a unique transcriptomic signature, which was characterized by the enrichment of orthologous cell cycle genes and a lower expression of genes responsible for neuroinflammation and phagocytosis. Their gene signatures were also distinct from that of known disease-associated microglia. The proliferation of quiescent\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>high<\/jats:sup>\n                    <\/jats:italic>\n                    microglia was evoked by pathological \u03b1-synuclein. Following the transplantation in the adult brain with the depletion of endogenous microglia,\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>high<\/jats:sup>\n                    <\/jats:italic>\n                    microglia grafts showed higher survival rates than their\n                    <jats:italic>Cspg4<\/jats:italic>\n                    <jats:sup>\u2212<\/jats:sup>\n                    \u00a0counterparts. Consistently,\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>high<\/jats:sup>\n                    <\/jats:italic>\n                    microglia were detected in the brain of AD patients and displayed the expansion in animal models of AD. These findings suggest that\n                    <jats:italic>\n                      Cspg4\n                      <jats:sup>high<\/jats:sup>\n                    <\/jats:italic>\n                    microglia are one of the origins of microgliosis during neurodegeneration and may open up a avenue for the treatment of neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2210643120","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T13:47:49Z","timestamp":1676555269000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["<i>\n                      Cspg4\n                      <sup>high<\/sup>\n                    <\/i>\n                    microglia contribute to microgliosis during neurodegeneration"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-7047","authenticated-orcid":false,"given":"Ya-jing","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-5091","authenticated-orcid":false,"given":"Yu","family":"Ding","sequence":"additional","affiliation":[{"name":"Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-qing","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-6514","authenticated-orcid":false,"given":"Hui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Hu","sequence":"additional","affiliation":[{"name":"Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-9178","authenticated-orcid":false,"given":"Jia-wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Co-innovation Center of Neuroregeneration, School of Medicine, Nantong University, Nantong, Jiangsu 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30499-X"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0051-5"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23612"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092132"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.066"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0335-3"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.007"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00651-6"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01456-w"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2010"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0242-x"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00875-2"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.11.004"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.018"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-01016-2"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.10.001"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.021"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0244-x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(81)80018-8"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.114.2.359"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","unstructured":"Y. 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