{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T20:21:47Z","timestamp":1771618907810,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,18]]},"group-title":"Cell Biology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Classical myeloproliferative neoplasms (MPN)\u2014essential thrombocythemia, polycythemia vera, and primary myelofibrosis\u2014are characterized by clonal hematopoiesis, overproduction of mature blood cells, and a high burden of thromboembolic events. Although thrombosis is the leading cause of morbidity and mortality in MPN, the contribution of the vascular endothelium remains incompletely defined. We investigated patient-derived endothelial colony-forming cells (ECFCs) as a surrogate for vascular endothelium in individuals with JAK2 V617F\u2013mutated MPN.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>ECFCs were cultured from peripheral blood of patients with MPN and healthy controls, phenotyped for thrombo-inflammatory and adhesive markers, tested for JAK2 V617F, and profiled by bulk RNA sequencing. Functional assays assessed endothelial-dependent factor Xa generation. Transcriptomes were benchmarked against public HUVEC reference datasets processed through an identical quantification pipeline.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ECFCs were obtained more frequently and in greater numbers from patients with MPN than from controls, indicating enhanced endothelial regenerative or activation potential. MPN ECFCs exhibited increased von Willebrand factor and P-selectin expression and release, along with elevated endothelial cell\u2013dependent factor Xa generation, consistent with a thrombo-inflammatory, procoagulant phenotype. JAK2 V617F was not detected in any ECFC colonies, supporting a non-clonal origin of these endothelial abnormalities. Transcriptomic analysis identified 289 differentially expressed genes in MPN versus control ECFCs, with pathway enrichment revealing coordinated dysregulation of blood coagulation, platelet activation, plasminogen regulation, vascular permeability, extracellular matrix organization, and angiogenesis. Benchmarking against HUVEC datasets confirmed strong endothelial identity of ECFC-derived cells, with MPN-associated changes reflecting endothelial activation rather than loss of endothelialness.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ECFCs from patients with JAK2-mutated MPN display functional and transcriptomic signatures of endothelial dysfunction in the absence of detectable driver mutations. These findings support a model in which a primed, thrombo-inflammatory endothelium cooperates with clonal hematopoiesis to promote the heightened thrombotic risk characteristic of MPN.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.16.706250","type":"posted-content","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T20:35:17Z","timestamp":1771446917000},"source":"Crossref","is-referenced-by-count":0,"title":["Thrombo-inflammatory endothelial signatures in\n                  <i>JAK2<\/i>\n                  -mutated myeloproliferative neoplasms"],"prefix":"10.64898","author":[{"given":"Salma A.S.","family":"Abosabie","sequence":"first","affiliation":[{"name":"Section of Hematology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Institute of Experimental Biomedicine, University Hospital Wuerzburg, Wuerzburg, Bavaria, Germany"},{"name":"Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius Maximilians 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