{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:38:57Z","timestamp":1790113137374,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2025,9]]},"abstract":"Abstract<\/jats:title>\n \n Platelets are anucleate cells produced in the bone marrow and derived from large progenitor cells called megakaryocytes (MKs). Platelets receive RNA transcripts from their progenitorial MKs during thrombopoiesis. However, the correspondence between platelet and MK transcriptomes is poorly understood, particularly in the context of germline mutations that cause platelet formation defects or thrombocytopenia. We have studied the effects of two such mutations on MK and platelet transcriptomes. We generated immortalized MK cell line (imMKCL)\u2010based models of Bernard\u2013Soulier syndrome and\n IKZF5<\/jats:italic>\n \u2010related thrombocytopenia. MKs derived from imMKCLs with either a homozygous deletion of\n GP9<\/jats:italic>\n (\n GP9<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ) or a heterozygous Y121F variant in\n IKZF5<\/jats:italic>\n (\n IKZF5<\/jats:italic>\n WT\/Y121F<\/jats:sup>\n ) exhibited reduced proplatelet formation (reductions of 96% and 57%, respectively). Platelets from patients with either\n GP9<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n or\n IKZF5<\/jats:italic>\n WT\/Y121F<\/jats:sup>\n genotypes had broad transcriptomic dysregulation, suggesting that (pro)platelet formation defects due to mutations in glycoprotein receptor and transcription factor genes such as\n GP9<\/jats:italic>\n and\n IKZF5<\/jats:italic>\n already affect the MK transcriptome. RNA\u2010seq data from MKs at four stages of differentiation revealed widespread but distinct changes in expression over time between the\n GP9<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n and the\n IKZF5<\/jats:italic>\n WT\/Y121F<\/jats:sup>\n genotypes. Dysregulated genes in\n GP9<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n MKs were enriched for RNA metabolism and actin\/tubulin folding pathways, whereas those in\n IKZF5<\/jats:italic>\n WT\/Y121F<\/jats:sup>\n MKs were enriched for cell cycle pathways. Most of these genes were also dysregulated in the platelets of patients with the corresponding diseases. Our results suggest that patients with inherited forms of thrombocytopenia present with specific transcriptomic changes during platelet formation.\n <\/jats:p>","DOI":"10.1002\/hem3.70217","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:40:56Z","timestamp":1758786056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transcriptome profiling of megakaryocytes and platelets: Application to\n GP9<\/i>\n \u2010 and\n IKZF5<\/i>\n \u2010related thrombocytopenia"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-3024","authenticated-orcid":false,"given":"Koenraad","family":"De Wispelaere","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences Center for Molecular and Vascular Biology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Ver 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