biostudies-literatureSun SNovo Nordisk Foundation Center for Stem Cell Medicine (reNEW)2156-2166https://www.ebi.ac.uk/biostudies/studies/S-EPMC9481898biostudies-literatureUnknown17(9)Human macrophages are a natural host of many mycobacterium species, including Mycobacterium abscessus (M. abscessus), an emerging pathogen affecting immunocompromised and cystic fibrosis patients with few available treatments. The search for an effective treatment is hindered by the lack of a tractable in vitro intracellular infection model. Here, we established a reliable model for M. abscessus infection using human pluripotent stem cell-derived macrophages (hPSC-macrophages). hPSC differentiation permitted reproducible generation of functional macrophages that were highly susceptible to M. abscessus infection. Electron microscopy demonstrated that M. abscessus was present in the hPSC-macrophage vacuoles. RNA sequencing analysis revealed a time-dependent host cell response, with differingStem cell reportsHuman pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection.PMC9481898reNEW MCRISee MRamialison MSutton PSarkar SStanley EGHidalgo ASun SNim HTStrumila KNg ESElefanty AGfalseHuman pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection.Human macrophages are a natural host of many mycobacterium species, including Mycobacterium abscessus (M. abscessus), an emerging pathogen affecting immunocompromised and cystic fibrosis patients with few available treatments. The search for an effective treatment is hindered by the lack of a tractable in vitro intracellular infection model. Here, we established a reliable model for M. abscessus infection using human pluripotent stem cell-derived macrophages (hPSC-macrophages). hPSC differentiation permitted reproducible generation of functional macrophages that were highly susceptible to M. abscessus infection. Electron microscopy demonstrated that M. abscessus was present in the hPSC-macrophage vacuoles. RNA sequencing analysis revealed a time-dependent host cell response, with differing2022-01-01T00:00:00Z2022 Sep2026-05-28T05:41:48.274Z2025-02-19T04:39:05.25ZS-EPMC94818983598533310.1016/j.stemcr.2022.07.013