{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T11:00:05Z","timestamp":1775905205357,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102019\u201004533"],"award-info":[{"award-number":["RGPIN\u20102019\u201004533"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000190","name":"University of Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Microglia\u2014the predominant immune cell of the central nervous system (CNS)\u2014possess an astounding capacity for proliferation. In development, this proliferation ensures that microglia are present at a sufficient density to perform their vital functions throughout development and into adulthood. During diseases or following CNS injuries, microglial proliferation similarly promotes an increase in microglial density to respond to damage. However, the governing mechanisms for microglial proliferation remain unknown. While many factors have been suggested to promote microglial proliferation\u2014known as mitogens\u2014or to increase microglial densities both in\u00a0vitro and in\u00a0vivo, there has been no standardized comparison of these factors. Here, we screened 22 of these factors in serum\u2010free microglial cultures which more faithfully recapitulate in\u00a0vivo microglial biology. We confirmed three cytokines\u2014colony stimulating factor\u20102, interleukin\u20103 and tumor necrosis factor\u2010\u0251\u2014promote microglia proliferation. We similarly tested the remaining non\u2010mitogenic factors for an indirect ability to regulate microglial proliferation by conditioning media from other CNS cell lineages and measuring the capacity for conditioned media to promote microglial proliferation. Of the tested factors and lineages, only interleukin\u20101\u0251 and interleukin\u20101\u03b2 promoted the release of a microglial mitogen from astrocytes, which we confirmed to be CSF2. Together, we demonstrate that in standardized conditions, very few factors that were previously reported to promote microglial proliferation or increase microglial densities, are directly, or indirectly, mitogenic.<\/jats:p>","DOI":"10.1002\/glia.70150","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:30:58Z","timestamp":1773984658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Mediators Both Directly and Indirectly Promote Microglial Proliferation"],"prefix":"10.1002","volume":"74","author":[{"given":"Brady P.","family":"Hammond","sequence":"first","affiliation":[{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Hahn","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly V.","family":"Lee","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0264-8316","authenticated-orcid":false,"given":"Bradley J.","family":"Kerr","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"},{"name":"Multiple Sclerosis Centre, University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Anesthesiology and Pain Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1385-1464","authenticated-orcid":false,"given":"Jason R.","family":"Plemel","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"},{"name":"Multiple Sclerosis Centre, University of Alberta  Edmonton Alberta Canada"},{"name":"Division of Neurology, Department of Medicine University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Medical Microbiology and Immunology University of Alberta  Edmonton Alberta Canada"},{"name":"Li Ka Shing Institute of Virology  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.03.042"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23929"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.04.043"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)64444\u20106"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1715"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2021.101511"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7176"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.08.004"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120696"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000723\u2010x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.022"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12865\u2010020\u201000380\u2010x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2012.05.025"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/456857"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.074088"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.07.22.604699"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24047"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.204610"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1768"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100090\u20108"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.403"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.04.013"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970715)49:2<248::AID-JNR13>3.0.CO;2-X"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.006"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201041661\u20109"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.08.012"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2025.104152"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2007.05763.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003734\u20106"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010023\u201000756\u20104"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.11.018"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.06.006"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110647"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv379"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.06.038"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101747"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai7635"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20104652(200003)182:3<311::AID\u2010JCP1>3.0.CO;2\u20139"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232\u2010022\u201000201\u20101"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201016896\u20108"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444960"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151948"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010023\u201001423\u20103"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860\u201014.2014"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010022\u201000584\u20102"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.70150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/glia.70150","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.70150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T10:27:58Z","timestamp":1775903278000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.70150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/glia.70150"],"URL":"https:\/\/doi.org\/10.1002\/glia.70150","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]},"assertion":[{"value":"2025-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70150"}}