biostudies-literatureNemec KMNIA NIH HHSNIH Office of the DirectorNIAID NIH HHSNIMH NIH HHSThe Paul Allen Frontiers GroupBlavatnik Family FoundationNational Institute of Allergy and Infectious DiseasesNational Institute of HealthNINDS NIH HHSNIGMS NIH HHSNIH HHSNational Science FoundationEsther A. and Joseph Klingenstein FundRP102900https://www.ebi.ac.uk/biostudies/studies/S-EPMC12844908biostudies-literatureUnknown14Microglia, the brain's resident macrophages, can be reconstituted by surrogate cells - a process termed 'microglia replacement'. To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells. Furthermore, ER-Hoxb8 progenitors are readily transducible by virus and easily stored as stable, genetically manipulated cell lines. As a demonstration of this system's power foreLifeMicroglia replacement by ER-Hoxb8 conditionally immortalized macrophages provides insight into Aicardi-Goutieres syndrome neuropathology.PMC12844908R01AI139544Blavatnik Family FellowshipNIH T32 GM008076DGE-1845298GRT-00000774R01NS120960R15 NS133939Fellowship Award in NeuroscienceR01 AI139544R01 NS120960T32-AG-000255-26T32 GM008076DP5 OD036159DP5OD036159T32MH019112T32 MH019112R15NS133939R35GM138085R01 NS134651R35 GM138085R01NS134651T32 GM007170T32 AG000255Nemec KMUy GPurnell FSThaiss CAGuo XOon CHO'Reilly MLO'Brien CAElfayoumi BLombroso SIByerly LChaluvadi VSWilliamson APBennett MLBlank NRawat PWang QBennett FCYaqoob FBailis WAisenberg WHTemsamrit BfalseMicroglia replacement by ER-Hoxb8 conditionally immortalized macrophages provides insight into Aicardi-Goutieres syndrome neuropathology.Microglia, the brain's resident macrophages, can be reconstituted by surrogate cells - a process termed 'microglia replacement'. To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells. Furthermore, ER-Hoxb8 progenitors are readily transducible by virus and easily stored as stable, genetically manipulated cell lines. As a demonstration of this system's power for2026-01-01T00:00:00Z2026 Jan2026-07-14T21:03:49.846Z2026-06-25T03:08:16.632ZS-EPMC128449084158967110.7554/eLife.102900