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Progranulin haploinsufficiency, a leading genetic cause of familial FTD, disrupts lysosomal function, lipid metabolism, autophagy, and neuroimmune signaling across multiple cell types. Increasing evidence indicates that microglia are particularly sensitive to progranulin loss, exhibiting elevated complement activation that contributes to TDP-43 proteinopathy and neuronal dysfunction. Here, we investigate the biological role of restoring progranulin exclusively within microglia by transplanting human induced pluripotent stem cell-derived microglia (iMG) into progranulin (\n                  <jats:italic>Grn<\/jats:italic>\n                  )-deficient mice. We find that wild-type, but not\n                  <jats:italic>Grn<\/jats:italic>\n                  -deficient, human iMG restore brain-wide progranulin levels, normalize microglial transcriptional states, and ameliorate pathological, functional, and behavioral phenotypes associated with progranulin loss. Because microglia are the only source of progranulin in this system, these findings demonstrate that microglial progranulin is sufficient to restore key aspects of cellular, circuit, and behavioral homeostasis in a progranulin-deficient FTD model. More broadly, this work highlights a central, microglia-intrinsic role for progranulin in maintaining brain function and provides a framework for dissecting microglia-specific mechanisms across FTD and related neurodegenerative disorders.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Our study demonstrates that xenotransplantation of wild-type human iPSC-derived microglia into progranulin-deficient mice mitigates core neuropathological, network-level, and behavioral features of Frontotemporal Dementia.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.13.699312","type":"posted-content","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:25:19Z","timestamp":1768368319000},"source":"Crossref","is-referenced-by-count":1,"title":["Transplantation of Human IPSC-derived Microglia Ameliorates Neuropathology and Circuit Dysfunction in Progranulin-Deficient Mice"],"prefix":"10.64898","author":[{"given":"Hayk","family":"Davtyan","sequence":"first","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6645-6412","authenticated-orcid":false,"given":"Sarah","family":"Naguib","sequence":"additional","affiliation":[{"name":"Helen and Robert Appel Alzheimer\u2019s Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4169-3002","authenticated-orcid":false,"given":"Yuliya","family":"Voskobiynyk","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA"},{"name":"Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA"},{"name":"Memory & Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Chadarevian","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA"},{"name":"Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joia K.","family":"Capocchi","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, 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