{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T09:14:57Z","timestamp":1761815697788,"version":"build-2065373602"},"reference-count":59,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"crossref","award":["GGP20073"],"award-info":[{"award-number":["GGP20073"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione A.R.M.R. Aiuti Ricerca Malattie Rare ETS"},{"DOI":"10.13039\/501100004004","name":"University of Trento","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004004","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>ADAMTS13 is a metalloprotease that cleaves the von Willebrand factor and prevents pathological thrombosis. Severe genetic deficiency of ADAMTS13 causes congenital thrombotic thrombocytopenic purpura, a life-threatening thrombotic microangiopathy. Increasing evidence suggests that ADAMTS13 contributes to physiological processes beyond hemostasis, including vascular development and tissue homeostasis, but these functions remain poorly understood. To address this gap, we generated a transparent, multitransgenic adamts13i5 zebrafish model and began investigating the developmental and disease-related roles of ADAMTS13 in vivo.<\/jats:p>\n                  <jats:p>The adamts13i5 mutants recapitulated hallmark features of congenital thrombotic thrombocytopenic purpura, including erythrocyte fragmentation and schistocyte formation in adults. In larvae, ADAMTS13 loss unveiled a prothrombotic response to vascular injury, a phenotype masked in patients by thrombocytopenia. Mechanistically, ADAMTS13 deficiency impaired developmental vascular patterning, suppressed vegfa expression, and reduced macrophage number, accompanied by diminished inflammatory and pro-angiogenic signaling. ADAMTS13 loss disrupted hematopoietic homeostasis in adulthood, with myeloid expansion and lymphoid depletion in the kidney marrow. These findings establish ADAMTS13 as a multifaceted regulator of thrombosis, vascular development, inflammation, and hematopoietic lineage specification. The adamts13i5 zebrafish provides a powerful vertebrate model for dissecting the mechanisms of thrombotic thrombocytopenic purpura pathogenesis and identifying therapeutic strategies extending beyond hemostasis.<\/jats:p>","DOI":"10.1242\/bio.062265","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T12:41:48Z","timestamp":1759754508000},"source":"Crossref","is-referenced-by-count":0,"title":["Zebrafish model reveals developmental and hematopoietic functions of ADAMTS13"],"prefix":"10.1242","volume":"14","author":[{"given":"Samuele","family":"Sartori","sequence":"first","affiliation":[{"name":"Computational and Integrative Biology (CIBIO) 1 Department of Cellular , , 38123 University of Trento ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Babiloni Chust","sequence":"additional","affiliation":[{"name":"Computational and Integrative Biology (CIBIO) 1 Department of Cellular , , 38123 University of Trento ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Varinelli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS 2 , 24126 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Matt\u00e8","sequence":"additional","affiliation":[{"name":"Computational and Integrative Biology (CIBIO) 1 Department of Cellular , , 38123 University of Trento ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piera","family":"Trionfini","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS 2 , 24126 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Tomasoni","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS 2 , 24126 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-1781","authenticated-orcid":false,"given":"Lucia","family":"Poggi","sequence":"additional","affiliation":[{"name":"Computational and Integrative Biology (CIBIO) 1 Department of Cellular , , 38123 University of Trento ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"2025103005115804200_BIO062265C1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3390\/cells14020085","article-title":"ADAMTS13 improves endothelial function and reduces inflammation in diabetic retinopathy","volume":"14","author":"Abu El-Asrar","year":"2025","journal-title":"Cells"},{"key":"2025103005115804200_BIO062265C2","doi-asserted-by":"publisher","first-page":"e189266","DOI":"10.1172\/JCI189266","article-title":"Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromes","volume":"135","author":"Aluri","year":"2025","journal-title":"J. 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