{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:16:18Z","timestamp":1786115778001,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,2]]},"group-title":"Pathology","reference-count":24,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and smooth muscle cell accumulation, but the progenitor-like cells that contribute to this process remain incompletely defined.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We combined analyses of human pulmonary arterial hypertension lungs and experimental PH models with bulk and single-cell RNA sequencing, lineage tracing, inducible ablation of CD133\n                    <jats:sup>+<\/jats:sup>\n                    cells, and conditional deletion of Cxcr4 in CD133\n                    <jats:sup>+<\/jats:sup>\n                    cells.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    CD133 expression was markedly increased in human and experimental PH lungs. Transcriptomic analyses identified inflammatory, metabolic, chemokine-associated, and smooth muscle cell-like programs in CD133\n                    <jats:sup>+<\/jats:sup>\n                    cells from PH lungs. Lineage tracing showed that CD133\n                    <jats:sup>+<\/jats:sup>\n                    cells contributed to endothelial and smooth muscle cell compartments during experimental PH. Genetic ablation of CD133\n                    <jats:sup>+<\/jats:sup>\n                    cells attenuated hypoxia-induced PH and pulmonary vascular remodeling, whereas Cxcr4 deletion in CD133\n                    <jats:sup>+<\/jats:sup>\n                    cells reduced PH severity.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    CD133\n                    <jats:sup>+<\/jats:sup>\n                    progenitor cells are functional contributors to pulmonary vascular remodeling, and CXCR4 signaling mediates their pathogenic activity. Targeting pathogenic CD133\n                    <jats:sup>+<\/jats:sup>\n                    cell states or CXCL12\/CXCR4 signaling may provide a strategy to limit vascular remodeling in PH.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.29.741640","type":"posted-content","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:45:18Z","timestamp":1785775518000},"source":"Crossref","is-referenced-by-count":0,"title":["CD133\n                  <sup>+<\/sup>\n                  progenitor cells promote pulmonary hypertension through CXCR4 signaling"],"prefix":"10.64898","author":[{"given":"Zhiqing","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, Department of Medicine, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2614-5027","authenticated-orcid":false,"given":"Dan","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, Department of Medicine, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-9039","authenticated-orcid":false,"given":"Jingbo","family":"Dai","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology, Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Genetic Medicine and Nanotechnology Development Center (GeneMeNDer), Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1175-7109","authenticated-orcid":false,"given":"Xianming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology, Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Genetic Medicine and Nanotechnology Development Center (GeneMeNDer), Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-0339","authenticated-orcid":false,"given":"You-Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology, Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Genetic Medicine and Nanotechnology Development Center (GeneMeNDer), Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"},{"name":"Departments of Medicine and Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"},{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-7923","authenticated-orcid":false,"given":"Zhiyu","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, Department of Medicine, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080521452026000_2026.07.29.741640v1.1","doi-asserted-by":"crossref","unstructured":"Mocumbi A , et al. 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