{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:31:16Z","timestamp":1789507876737,"version":"build-2803163510"},"reference-count":94,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"18","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,5,5]]},"abstract":"<jats:p>\n            TMEM106B, a lysosomal transmembrane protein, has been closely associated with brain health. Recently, an intriguing link between TMEM106B and brain inflammation has been discovered, but how TMEM106B regulates inflammation is unknown. Here, we report that TMEM106B deficiency in mice leads to reduced microglia proliferation and activation and increased microglial apoptosis in response to demyelination. We also found an increase in lysosomal pH and a decrease in lysosomal enzyme activities in TMEM106B-deficient microglia. Furthermore, TMEM106B loss results in a significant decrease in the protein levels of TREM2, an innate immune receptor essential for microglia survival and activation. Specific ablation of TMEM106B in microglia results in similar microglial phenotypes and myelination defects in mice, supporting the idea that microglial TMEM106B is critical for proper microglial activities and myelination. Moreover, the\n            <jats:italic>TMEM106B<\/jats:italic>\n            risk allele is associated with myelin loss and decreased microglial numbers in humans. Collectively, our study unveils a previously unknown role of TMEM106B in promoting microglial functionality during demyelination.\n          <\/jats:p>","DOI":"10.1126\/sciadv.add2676","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T17:58:17Z","timestamp":1683309497000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":20,"title":["TMEM106B regulates microglial proliferation and survival in response to demyelination"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-5464","authenticated-orcid":true,"given":"Tingting","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilun","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuancheng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-9837","authenticated-orcid":true,"given":"Kenton","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Nunez Santos","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-9920","authenticated-orcid":true,"given":"Akshayakeerthi","family":"Arthanarisami","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alissa L.","family":"Nana","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San\u00a0Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna L.","family":"Jankowsky","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA."},{"name":"Departments of Molecular and Cellular Biology, Neurology, and Neurosurgery, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1410-2027","authenticated-orcid":true,"given":"William W.","family":"Seeley","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San\u00a0Francisco, CA 94158, USA."},{"name":"Department of Pathology, University of California, San\u00a0Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6447-9992","authenticated-orcid":true,"given":"Fenghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.350"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31820a0e3b"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.536"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1240-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1249-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1239-x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.06.023"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0782-y"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25486"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318264e3ac"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz099"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy029"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx314"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12811"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2017.02.009"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.02.026"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.03.032"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04670-9"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00665-3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04650-z"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds475"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0521-12.2012"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.365098"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2014.07.006"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.06.026"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05013-x"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa154"},{"key":"e_1_3_3_30_2","first-page":"450","article-title":"The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes","volume":"33","author":"Schwenk B. M.","year":"2014","unstructured":"B. M.\u00a0Schwenk, C. M.\u00a0Lang, S.\u00a0Hogl, S.\u00a0Tahirovic, D.\u00a0Orozco, K.\u00a0Rentzsch, S. F.\u00a0Lichtenthaler, C. C.\u00a0Hoogenraad, A.\u00a0Capell, C.\u00a0Haass, D.\u00a0Edbauer, The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes. EMBO J. 33, 450\u2013467 (2014).","journal-title":"EMBO J."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050219"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.060"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt247"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12903"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12945"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01334-7"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa141"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008775"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.016"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.03.006"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201709069"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.023"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0242-x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.003"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2459-16.2017"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00073"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00385.x"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00538-8"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070850"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00168-4"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3469"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09615"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2013.04.007"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00205-9"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.09.008"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02246-3"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.10.023"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77983"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1388-1"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199802)22:2<180::AID-GLIA9>3.0.CO;2-B"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.1.272"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1586-1"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh516"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.030"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05534-y"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0184-2"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000149"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-35"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2615-05.2006"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24754"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.041"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4547"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.01.027"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050197"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2021.02.003"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03988-3"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26201"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12451"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2021.09.003"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050241"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.12.007"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/75973"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2003.tb00032.x"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-4-23"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0845-8"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0616-08.2008"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700477114"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1098"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157022"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw419"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.add2676","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:36:47Z","timestamp":1704836207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.add2676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":94,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2023,5,5]]}},"alternative-id":["10.1126\/sciadv.add2676"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.add2676","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]},"assertion":[{"value":"2022-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadd2676"}}