{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:23:23Z","timestamp":1785435803481,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,28]]},"group-title":"Immunology","reference-count":93,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"crossref","award":["CZF2019-002452"],"award-info":[{"award-number":["CZF2019-002452"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI106697"],"award-info":[{"award-number":["AI106697"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI057266"],"award-info":[{"award-number":["AI057266"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["T32AI106711"],"award-info":[{"award-number":["T32AI106711"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P30CA013696"],"award-info":[{"award-number":["P30CA013696"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["P30DK132710"],"award-info":[{"award-number":["P30DK132710"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Human macrophages (M\u03a6s) reside in tissues and develop tissue-specific identities. While studies in mice have identified molecular signatures for site-specific M\u03a6 differentiation, we know less about the transcriptional profiles of human M\u03a6s in distinct sites, including mucosal tissues and lymphoid organs during homeostasis and activation. Here, we use multimodal single-cell sequencing and\n                  <jats:italic>ex vivo<\/jats:italic>\n                  stimulation assays to define tissue signatures for populations of human M\u03a6s isolated from lungs, small intestine, spleen, bone marrow, and lymph nodes obtained from individual organ donors. Our results reveal distinct tissue-adapted gene and protein profiles of metabolic, adhesion, and immune interaction pathways, which are specific to M\u03a6s and not monocytes isolated from the same sites. These signatures exhibit homology to murine M\u03a6s from the same sites. Tissue-adapted M\u03a6s remained responsive to polarizing cytokine stimuli\n                  <jats:italic>ex vivo<\/jats:italic>\n                  , with upregulation of expected transcripts and secreted proteins, while retaining tissue-specific profiles. Together, our findings show how human M\u03a6 identity is coupled to their site of residence for mucosal and lymphoid organs and is intrinsically maintained during activation and polarization.\n                <\/jats:p>","DOI":"10.1101\/2025.05.23.655632","type":"posted-content","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T13:25:17Z","timestamp":1748438717000},"source":"Crossref","is-referenced-by-count":0,"title":["Tissue signatures of human macrophages during homeostasis and activation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1500-8713","authenticated-orcid":false,"given":"Daniel P.","family":"Caron","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9198-7743","authenticated-orcid":false,"given":"William L.","family":"Specht","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-1857","authenticated-orcid":false,"given":"David","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5428-0683","authenticated-orcid":false,"given":"Steven B.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1603-761X","authenticated-orcid":false,"given":"Peter A.","family":"Szabo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-4837","authenticated-orcid":false,"given":"Peter A.","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA"},{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-9183","authenticated-orcid":false,"given":"Donna L.","family":"Farber","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA"},{"name":"Department of Surgery, Columbia University Irving Medical 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