biostudies-literatureShan QStrategic Priority Research Program of the Chinese Academy of SciencesJoint Innovation Team for Clinical & Basic ResearchNational Key R&D Program of ChinaMajor Project of Guangzhou National LaboratoryNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaYouth Innovation Promotion Association of the Chinese Academy of Sciencese07293https://www.ebi.ac.uk/biostudies/studies/S-EPMC12910429biostudies-literatureUnknown22(10)The heterogeneity of pulmonary cells affects their response to inhaled fine particles. However, the most critical responder cells in particle exposure still remain controversial, and their functional heterogeneity warrants detailed exploration. Herein, a gold nanoparticle model dual-labeled with sulfo-cyanine3 and Tag RNAs is developed, aiming to capture prominent fine particle-responsive cell subpopulations using fluorescence-activated cell sorting and single-cell RNA sequencing. Alveolar macrophages (AMs), recruited macrophages (recMacs), and interstitial macrophages (IMs) exhibited the strongest responsiveness to particles, among which 14 subsets are identified with partially overlapping yet distinct functions. Notably, AMs_3, AMs_7, and recMacs_4 subsets are highlighted in the particleSmall (Weinheim an der Bergstrasse, Germany)Deciphering the Heterogeneity of Pulmonary Macrophages in Response to Fine Particles.PMC1291042922406113220210032024YFA1210902224226102022042XDB0750000202407GZNL2024A01028Liu YRen JDong ZQi YShan QXu FMa JLiu SZhang SLi NZhou ZLiu WfalseDeciphering the Heterogeneity of Pulmonary Macrophages in Response to Fine Particles.The heterogeneity of pulmonary cells affects their response to inhaled fine particles. However, the most critical responder cells in particle exposure still remain controversial, and their functional heterogeneity warrants detailed exploration. Herein, a gold nanoparticle model dual-labeled with sulfo-cyanine3 and Tag RNAs is developed, aiming to capture prominent fine particle-responsive cell subpopulations using fluorescence-activated cell sorting and single-cell RNA sequencing. Alveolar macrophages (AMs), recruited macrophages (recMacs), and interstitial macrophages (IMs) exhibited the strongest responsiveness to particles, among which 14 subsets are identified with partially overlapping yet distinct functions. Notably, AMs_3, AMs_7, and recMacs_4 subsets are highlighted in the particle2026-01-01T00:00:00Z2026 Feb2026-07-16T00:44:37.844Z2026-07-09T10:25:53.6ZS-EPMC129104294150408010.1002/smll.202507293