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Although many molecular regulators of efferocytosis have been defined, less is known about whether macrophages can be reprogrammed into a distinct cellular state with intrinsically enhanced efferocytosis capacity. Guided by a CRISPR screen, we found that\n                  <jats:italic>Pdcd6ip<\/jats:italic>\n                  loss induces cytokinesis arrest and binucleation, creating macrophages with superior efferocytic function. Binucleated\n                  <jats:italic>\n                    Pdcd6ip\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  bone marrow-derived macrophages demonstrate a coordinately enhanced multi-corpse capture and processing, and resolution response, and acquired a distinct transcriptomic signature.\n                  <jats:italic>In vivo<\/jats:italic>\n                  ,\n                  <jats:italic>Pdcd6ip<\/jats:italic>\n                  deletion enhanced splenic macrophage efferocytosis, reduced autoimmune responses after repeated apoptotic cell challenge, and promoted plaque stability without metabolic or hematologic changes.\n                  <jats:italic>PDCD6IP<\/jats:italic>\n                  perturbation similarly increased binucleation and engulfment in human macrophage-like cells. Thus, incomplete cytokinesis represents an unrecognized route to macrophage specialization with enhanced efferocytosis capacity.\n                <\/jats:p>","DOI":"10.64898\/2026.08.10.731793","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:45:11Z","timestamp":1786463111000},"source":"Crossref","is-referenced-by-count":0,"title":["Cytokinesis Arrest-induced Binucleation of Macrophages Produces Highly Efficient Efferocytes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0742-7459","authenticated-orcid":false,"given":"Xun","family":"Wu","sequence":"first","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyi","family":"Xue","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9180-3615","authenticated-orcid":false,"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8303-3191","authenticated-orcid":false,"given":"Jinnan","family":"Yue","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Shern","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Cui","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Wu","sequence":"additional","affiliation":[{"name":"Columbia Stem Cell Initiative, Flow Core, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kissner","sequence":"additional","affiliation":[{"name":"Columbia Stem Cell Initiative, Flow Core, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"Institute of Molecular Vascular Medicine, TUM Klinikum, Technical University Munich, Munich, Germany"},{"name":"German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Berlin, Germany"},{"name":"Department of Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Tabas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"},{"name":"Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"},{"name":"Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Tall","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-938X","authenticated-orcid":false,"given":"Hanrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiometabolic Genomics Program, Division of Cardiology, 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