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Fracture healing is regulated, in part, by the balance of proinflammatory and anti\u2010inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single\u2010cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (<jats:italic>n<\/jats:italic>\u2009=\u20095) or from native bone controls when harvesting autologous bone graft (<jats:italic>n<\/jats:italic>\u2009=\u20094). Cells within the samples were isolated and analyzed using the Chromium Single\u2010Cell System (10x Genomics\u00a0Inc.) and Illumina sequencers. Twenty\u2010three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14\u2009+\u2009dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14\u2009+\u2009DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human\u2010derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single\u2010cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and\/or investigation into therapeutic options.<\/jats:p>","DOI":"10.1002\/jor.25452","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T13:26:58Z","timestamp":1666013218000},"page":"1060-1069","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Single\u2010cell RNAseq provides insight into altered immune cell populations in human fracture nonunions"],"prefix":"10.1002","volume":"41","author":[{"given":"Keith G.","family":"Avin","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, School of Health and Human Sciences Indiana University Indianapolis Indiana USA"},{"name":"Division of Nephrology, School of Medicine Indiana University Indianapolis Indiana 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