title: Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages.
abstract: Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and alveoli where they maintain host defense and promote alveolar homeostasis by ingesting inhaled particulates and regulating inflammatory responses. Recent studies have demonstrated that AMs populate the lungs during embryogenesis and self-renew throughout life with minimal replacement by circulating monocytes, except under extreme conditions of depletion or radiation injury. Here we demonstrate that on a global scale, environment appears to dictate AM development and function. Indeed, transcriptome analysis of embryonic host-derived and postnatal donor-derived AMs coexisting within the same mouse demonstrated >98% correlation and overall functional analyses were similar. However, we also identified several genes whose expression was dictated by origin rather than environment. The most differentially expressed gene not altered by environment was Marco, a gene recently demonstrated to have enhancer activity in embryonic-derived but not postnatal-derived tissue macrophages. Overall, we show that under homeostatic conditions, the environment largely dictates the programming and function of AMs, whereas the expression of a small number of genes remains linked to the origin of the cell.
authors.affiliation: Department of Pediatrics.
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Gibbings
authors.affiliation: Department of Pediatrics.
authors.forename: Rajni
authors.initials: R
authors.lastname: Goyal
authors.affiliation: Department of Immunology and Microbiology.
authors.forename: A Nicole
authors.initials: AN
authors.lastname: Desch
authors.affiliation: Integrated Center for Genes, Environment, and Health, and.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Leach
authors.affiliation: Department of Pediatrics.
authors.forename: Miglena
authors.initials: M
authors.lastname: Prabagar
authors.affiliation: Department of Pediatrics.
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Atif
authors.affiliation: Department of Pediatrics.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Bratton
authors.affiliation: Department of Medicine, National Jewish Health and University of Colorado Denver Anschutz Campus, Denver, CO.
authors.forename: William
authors.initials: W
authors.lastname: Janssen
authors.affiliation: Department of Pediatrics, Department of Immunology and Microbiology.
authors.forename: Claudia V
authors.initials: CV
authors.lastname: Jakubzick
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000235:genetics; D060833:Cellular Microenvironment / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D018836:Inflammation Mediators / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000235:genetics; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics; D018183:Transplantation Chimera
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C092228:Marco protein, mouse; D011971:Receptors, Immunologic