{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:33:50Z","timestamp":1793010830300,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008572","name":"University of Ottawa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008572","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Male cancer patients are 30% more likely to develop cachexia compared to females; however, the underlying aetiology remains unknown. Myelopoiesis induces inflammation in cancer cachexia, which contributes to muscle atrophy. Whether differences in myelopoiesis during cancer cachexia initiation contribute to sex\u2010based differences in cachexia incidence remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male and female C57BL\/6 and B6(C)\u2010Ccr2\n                      <jats:sup>tm1.1Cln<\/jats:sup>\n                      \/J mice were randomized into sham (PBS) or were inoculated subcutaneously with Lewis lung carcinoma (LLC) to induce cachexia. Mice were sacrificed 2 (14\u2009days), 2.5 (17\u2009days) and 3.5\u2009weeks (24\u2009days) post\u2010inoculation. Changes in body composition, haematopoietic stem and progenitor cells (HSPCs), myeloid immune cell migration, bone marrow niche cellular dynamics and CCL2 expression were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LLC inoculation reduced tumour\u2010free body weight, lean mass, gastrocnemius\u2013soleus mass and myofiber cross\u2010sectional area (CSA) in males at 3.5\u2009weeks (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), while females maintained tumour\u2010free body weight, lean mass and CSA. Within the bone marrow, haematopoietic stem cells (HSCs) were increased at 2, 2.5 and 3.5\u2009weeks compared to sham in males and at 2.5\u2009weeks compared to 2 and 3.5\u2009weeks in females (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Multipotent progenitors (MPPs) were significantly increased at 2, 2.5 and 3.5\u2009weeks compared to sham in males and at 2.5\u2009weeks compared to sham, 2 and 3.5\u2009weeks in females (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Downstream, common myeloid progenitors (CMPs) and granulocyte\u2010monocyte progenitors (GMPs) were elevated in males at 2.5\u2009weeks, with CCR2\n                      <jats:sup>+<\/jats:sup>\n                      GMPs peaking at 2.5\u2009weeks in males and 3.5\u2009weeks in females (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Sex differences in HSC niche composition were also observed with osteoprogenitors, osteoblasts and endothelial cells increased at 2\u2009weeks in males, while females showed increased osteoprogenitors and endothelial progenitors at 2.5\u2009weeks in tumour\u2010bearing mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Plasma C\u2010C motif chemokine ligand 2 (CCL2) concentrations increased with tumour progression in both sexes; however, CCR2\n                      <jats:sup>+<\/jats:sup>\n                      \u2010progenitors and macrophages were decreased at 2.5 and 3.5\u2009weeks compared to 2\u2009weeks (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In skeletal muscle, CCL2 concentration increased at 3.5\u2009weeks, and the proportion of CCR2\n                      <jats:sup>+<\/jats:sup>\n                      \/CD206\n                      <jats:sup>\u2212<\/jats:sup>\n                      macrophages increased, while total macrophage abundance remained unchanged (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Macrophage subpopulations were related to decreasing CSA in males but not females.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study suggests that aberrant myelopoiesis and sex\u2010specific HSC niche remodelling precede muscle atrophy during cachexia development in males. These findings provide an important first step in understanding the role aberrant myelopoiesis plays in cancer cachexia and establish myeloid skewing as a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70403","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:27:45Z","timestamp":1792142865000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aberrant Myelopoiesis and Haematopoietic Stem Cell Niche Remodelling Precedes Cancer Cachexia Onset in a Sex\u2010Dependent Manner"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9005-8718","authenticated-orcid":false,"given":"Alice","family":"Tate","sequence":"first","affiliation":[{"name":"School of Human Kinetics, Faculty of Health Science University of Ottawa  Ottawa 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