{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:32:00Z","timestamp":1788388320236,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades","award":["B-CTS-676-UGR"],"award-info":[{"award-number":["B-CTS-676-UGR"]}]},{"DOI":"10.13039\/501100003329","name":"Ministry of Economy and Competitiveness","doi-asserted-by":"publisher","award":["PID2023-152099OB-I00"],"award-info":[{"award-number":["PID2023-152099OB-I00"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Roberto Arnall"},{"name":"ROLUCAN Association"},{"name":"Predoctoral Recruitment of Research Trainees-Predoctoral student","award":["PREDOC_01765"],"award-info":[{"award-number":["PREDOC_01765"]}]},{"name":"Spanish Health Institute Carlos III","award":["FI17\/00178"],"award-info":[{"award-number":["FI17\/00178"]}]},{"DOI":"10.13039\/501100023561","name":"Ministry of Universities","doi-asserted-by":"crossref","award":["FPU18\/03410"],"award-info":[{"award-number":["FPU18\/03410"]}],"id":[{"id":"10.13039\/501100023561","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Platelets and their extracellular vesicles (EVs) have emerged as promising liquid biopsy biosources for cancer detection and monitoring. The megakaryoblastic MEG-01 cell line offers a controlled system for generating platelet-like particles (PLPs) and EVs through valproic-acid-induced differentiation. Here, we performed comprehensive characterization and proteomic validation of MEG-01-derived populations, native human platelets, and their EVs using nanoparticle tracking analysis, transmission electron microscopy, imaging flow cytometry and quantitative proteomics. MEG-01 megakaryocytic differentiation is characterized by polylobulated nuclei, proplatelet formation, and elevated CD41\/CD42a expression. PLPs predominantly exhibit an activated-like phenotype (CD62P+, degranulated morphology), while microvesicles (100\u2013500 nm) and exosomes (50\u2013250 nm) displayed size distributions and phenotypic markers consistent with native platelet-derived EVs. Proteomics identified substantial core proteomes shared across fractions and fraction-specific patterns consistent with selective cargo partitioning during EV biogenesis. Functional enrichment indicated that MEG-01-derived vesicles preserve key hemostatic, cytoskeletal, and immune pathways commonly associated with platelet EV biology. Ingenuity Pathway Analysis showed that PLPs exhibit proliferative transcriptional programs (elevated MYC\/RB1\/TEAD1, reduced GATA1), while plasma exosomes display minimal differential pathway activation compared to MEG-01 exosomes. Overall, these findings suggest that MEG-01-derived EVs approximate certain aspects of megakaryocyte-lineage exosomes and activated platelet-like states, although they do not fully replicate native platelet biology. Notably, plasma exosomes show strong proteomic convergence with MEG-01 exosomes, whereas platelet exosomes retain distinct activation-related features.<\/jats:p>","DOI":"10.3390\/biom15121698","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T10:50:38Z","timestamp":1764931838000},"page":"1698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic Validation of MEG-01-Derived Extracellular Vesicles as Representative Models for Megakaryocyte- and Platelet-Derived Extracellular Vesicles"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-5132","authenticated-orcid":false,"given":"Jose Manuel","family":"Sanchez-Manas","sequence":"first","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-5033","authenticated-orcid":false,"given":"Sonia","family":"Perales","sequence":"additional","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-0005","authenticated-orcid":false,"given":"Gonzalo","family":"Martinez-Navajas","sequence":"additional","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0304-221X","authenticated-orcid":false,"given":"Jorge","family":"Ceron-Hernandez","sequence":"additional","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"},{"name":"Liquid Biopsies and Cancer Interception Group, PTS, Ganada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-3106","authenticated-orcid":false,"given":"Cristina M.","family":"Lopez","sequence":"additional","affiliation":[{"name":"IMIBIC Mass Spectrometry and Molecular Imaging Unit, Maimonides, Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of C\u00f3rdoba, Avenida Men\u00e9ndez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7939-0029","authenticated-orcid":false,"given":"Angela","family":"Peralbo-Molina","sequence":"additional","affiliation":[{"name":"IMIBIC Mass Spectrometry and Molecular Imaging Unit, Maimonides, Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of C\u00f3rdoba, Avenida Men\u00e9ndez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan R.","family":"Delgado","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. GRANADA, 18012 Granada, Spain"},{"name":"Department of Medical Oncology, Virgen de las Nieves University Hospital, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6814-2748","authenticated-orcid":false,"given":"Joaquina","family":"Martinez-Galan","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. GRANADA, 18012 Granada, Spain"},{"name":"Department of Medical Oncology, Virgen de las Nieves University Hospital, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8013-4273","authenticated-orcid":false,"given":"Veronica","family":"Ramos-Mejia","sequence":"additional","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Cellular Biology, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9481-9628","authenticated-orcid":false,"given":"Eduardo","family":"Chicano-Galvez","sequence":"additional","affiliation":[{"name":"IMIBIC Mass Spectrometry and Molecular Imaging Unit, Maimonides, Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of C\u00f3rdoba, Avenida Men\u00e9ndez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-7841","authenticated-orcid":false,"given":"Maria","family":"Hernandez-Valladares","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. GRANADA, 18012 Granada, Spain"},{"name":"Department of Physical Chemistry, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-1753","authenticated-orcid":false,"given":"Francisco M.","family":"Ortuno","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering, Automatics and Robotics, C.I.T.I.C., University of Granada, Calle Periodista Rafael G\u00f3mez Montero 2, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-6884","authenticated-orcid":false,"given":"Carolina","family":"Torres","sequence":"additional","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. GRANADA, 18012 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Av. Doctor Jes\u00fas Candel F\u00e1bregas 11, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-5353","authenticated-orcid":false,"given":"Pedro J.","family":"Real","sequence":"additional","affiliation":[{"name":"Gene Regulation, Stem Cells and Development Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Avenida Fuentenueva s\/n, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102774","DOI":"10.1016\/j.ctrv.2024.102774","article-title":"Liquid Biopsy: An Arsenal for Tumour Screening and Early Diagnosis","volume":"129","author":"Zhang","year":"2024","journal-title":"Cancer Treat. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1161\/ATVBAHA.120.314644","article-title":"Platelet Extracellular Vesicles: Beyond the Blood","volume":"41","author":"Puhm","year":"2021","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ccell.2015.09.018","article-title":"RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics","volume":"28","author":"Best","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117690","DOI":"10.1016\/j.cca.2023.117690","article-title":"Tumor-Educated Platelets","volume":"552","author":"Najafi","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular Vesicles as Tools and Targets in Therapy for Diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhuang, T., Wang, S., Yu, X., He, X., Guo, H., and Ou, C. (2024). Current Status and Future Perspectives of Platelet-Derived Extracellular Vesicles in Cancer Diagnosis and Treatment. Biomark. Res., 12.","DOI":"10.1186\/s40364-024-00639-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102356","DOI":"10.1016\/j.rpth.2024.102356","article-title":"Heterogeneity of Platelets and Their Responses","volume":"8","author":"Thomas","year":"2024","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kaiser, R., Anjum, A., and Nicolai, L. (2025). Platelet Heterogeneity in Disease\u2014The Many and the Diverse?. Blood.","DOI":"10.1182\/blood.2025028957"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liu, H., Liu, J., Wang, L., and Zhu, F. (2021). In Vitro Generation of Megakaryocytes and Platelets. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.713434"},{"key":"ref_10","first-page":"1500","article-title":"New Insights into the Generation and Function of Megakaryocytes in Health and Disease","volume":"110","author":"Du","year":"2025","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s44313-025-00071-9","article-title":"Cell-Based Artificial Platelet Production: Historical Milestones, Emerging Trends, and Future Directions","volume":"60","author":"Kim","year":"2025","journal-title":"Blood Res."},{"key":"ref_12","first-page":"947","article-title":"Latest Culture Techniques: Cracking the Secrets of Bone Marrow to Mass-Produce Erythrocytes and Platelets Ex Vivo","volume":"106","author":"Aguilar","year":"2021","journal-title":"Haematologica"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1038\/ncomms5372","article-title":"Direct Induction of Haematoendothelial Programs in Human Pluripotent Stem Cells by Transcriptional Regulators","volume":"5","author":"Elcheva","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/mt.2014.196","article-title":"SCL\/TAL1-Mediated Transcriptional Network Enhances Megakaryocytic Specification of Human Embryonic Stem Cells","volume":"23","author":"Toscano","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1186\/s13287-018-1074-z","article-title":"MEIS2 Regulates Endothelial to Hematopoietic Transition of Human Embryonic Stem Cells by Targeting TAL1","volume":"9","author":"Wang","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-1-4939-8585-2_10","article-title":"Differentiation of Human Pluripotent Stem Cells to Megakaryocytes by Transcription Factor-Driven Forward Programming","volume":"1812","author":"Moreau","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.stem.2014.01.011","article-title":"Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells","volume":"14","author":"Nakamura","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14458","DOI":"10.1073\/pnas.241427398","article-title":"Induction of Platelet Formation from Megakaryocytoid Cells by Nitric Oxide","volume":"98","author":"Battinelli","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Davies, R., Allen, S., Mennan, C., Platt, M., Wright, K., and Kehoe, O. (2023). Extracellular Vesicle Depletion Protocols of Foetal Bovine Serum Influence Umbilical Cord Mesenchymal Stromal Cell Phenotype, Immunomodulation, and Particle Release. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119242"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"648","DOI":"10.3109\/09537104.2010.513748","article-title":"Valproic Acid and All Trans Retinoic Acid Differentially Induce Megakaryopoiesis and Platelet-like Particle Formation from the Megakaryoblastic Cell Line MEG-01","volume":"21","author":"Schweinfurth","year":"2010","journal-title":"Platelets"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Do Minh, A., Star, A.T., Stupak, J., Fulton, K.M., Haqqani, A.S., G\u00e9linas, J.-F., Li, J., Twine, S.M., and Kamen, A.A. (2021). Characterization of Extracellular Vesicles Secreted in Lentiviral Producing HEK293SF Cell Cultures. Viruses, 13.","DOI":"10.20944\/preprints202103.0696.v1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41596-018-0082-x","article-title":"Single-Pot, Solid-Phase-Enhanced Sample Preparation for Proteomics Experiments","volume":"14","author":"Hughes","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1093\/bioinformatics\/bth327","article-title":"Faster Cyclic Loess: Normalizing RNA Arrays via Linear Models","volume":"20","author":"Ballman","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1002\/imt2.43","article-title":"Complex Heatmap Visualization","volume":"1","author":"Gu","year":"2022","journal-title":"iMeta"},{"key":"ref_26","first-page":"3221","article-title":"Accelerating T-SNE Using Tree-Based Algorithms","volume":"15","year":"2014","journal-title":"J. Mach. Learn. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the Unification of Biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gene Ontology Consortium, Aleksander, S.A., Balhoff, J., Carbon, S., Cherry, J.M., Drabkin, H.J., Ebert, D., Feuermann, M., Gaudet, P., and Harris, N.L. (2023). The Gene Ontology Knowledgebase in 2023. Genetics, 224, iyad031.","DOI":"10.1093\/genetics\/iyad031"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Huang, R., Grishagin, I., Wang, Y., Zhao, T., Greene, J., Obenauer, J.C., Ngan, D., Nguyen, D.-T., Guha, R., and Jadhav, A. (2019). The NCATS BioPlanet\u2014An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00445"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Garcia-Moreno, A., L\u00f3pez-Dom\u00ednguez, R., Villatoro-Garc\u00eda, J.A., Ramirez-Mena, A., Aparicio-Puerta, E., Hackenberg, M., Pascual-Montano, A., and Carmona-Saez, P. (2022). Functional Enrichment Analysis of Regulatory Elements. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030590"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal Analysis Approaches in Ingenuity Pathway Analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1172\/JCI26891","article-title":"The Biogenesis of Platelets from Megakaryocyte Proplatelets","volume":"115","author":"Patel","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1146\/annurev-biochem-100924-012717","article-title":"Extracellular Vesicles and Cellular Homeostasis","volume":"94","author":"Ngo","year":"2025","journal-title":"Annu. Rev. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1101\/gad.301184.117","article-title":"Transcriptional Integration of Mitogenic and Mechanical Signals by Myc and YAP","volume":"31","author":"Croci","year":"2017","journal-title":"Genes. Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15601","DOI":"10.1073\/pnas.1010564107","article-title":"Altered mRNA Transport, Docking, and Protein Translation in Neurons Lacking Fragile X Mental Retardation Protein","volume":"107","author":"Kao","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","unstructured":"(2025, October 23). A Comparison of Methods for the Isolation and Separation of Extracellular Vesicles from Protein and Lipid Particles in Human Serum|Scientific Reports. Available online: https:\/\/www.nature.com\/articles\/s41598-020-57497-7."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.aca.2019.09.022","article-title":"Fast Isolation of Highly Specific Population of Platelet-Derived Extracellular Vesicles from Blood Plasma by Affinity Monolithic Column, Immobilized with Anti-Human CD61 Antibody","volume":"1091","author":"Multia","year":"2019","journal-title":"Anal. Chim. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.exphem.2020.04.006","article-title":"Signaling Properties of Murine MPL and MPL Mutants after Stimulation with Thrombopoietin and Romiplostim","volume":"85","author":"Rommel","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1182\/blood-2018-11-884486","article-title":"Eltrombopag Maintains Human Hematopoietic Stem and Progenitor Cells under Inflammatory Conditions Mediated by IFN-\u03b3","volume":"133","author":"Alvarado","year":"2019","journal-title":"Blood"},{"key":"ref_41","unstructured":"(2025, October 21). Large-Scale Production of Megakaryocytes from Human Pluripotent Stem Cells by Chemically Defined Forward Programming|Nature Communications. Available online: https:\/\/www.nature.com\/articles\/ncomms11208."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.omtn.2023.06.008","article-title":"Lentiviral Gene Therapy Reverts GPIX Expression and Phenotype in Bernard-Soulier Syndrome Type C","volume":"33","author":"Simon","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1073\/pnas.0511150103","article-title":"Identification of Distinct Molecular Phenotypes in Acute Megakaryoblastic Leukemia by Gene Expression Profiling","volume":"103","author":"Bourquin","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1084\/jem.20100844","article-title":"Transient Activation of C-MYC Expression Is Critical for Efficient Platelet Generation from Human Induced Pluripotent Stem Cells","volume":"207","author":"Takayama","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6151","DOI":"10.1038\/sj.onc.1206641","article-title":"Low Molecular Weight Inhibitors of Myc-Max Interaction and Function","volume":"22","author":"Yin","year":"2003","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.18632\/oncotarget.1572","article-title":"Inhibition of BET Bromodomain Proteins as a Therapeutic Approach in Prostate Cancer","volume":"4","author":"Wyce","year":"2013","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eabl5654","DOI":"10.1126\/scitranslmed.abl5654","article-title":"Phenotypic Screening with Deep Learning Identifies HDAC6 Inhibitors as Cardioprotective in a BAG3 Mouse Model of Dilated Cardiomyopathy","volume":"14","author":"Yang","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1038\/s41467-017-01690-2","article-title":"Critical Role of the HDAC6-Cortactin Axis in Human Megakaryocyte Maturation Leading to a Proplatelet-Formation Defect","volume":"8","author":"Messaoudi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ceron-Hernandez, J., Martinez-Navajas, G., Sanchez-Manas, J.M., Molina, M.P., Xie, J., Aznar-Peralta, I., Garcia-Diaz, A., Perales, S., Torres, C., and Serrano, M.J. (2025). Oncogenic KRASG12D Transfer from Platelet-like Particles Enhances Proliferation and Survival in Non-Small Cell Lung Cancer Cells. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073264"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41565-024-01774-3","article-title":"Harnessing Extracellular Vesicle Heterogeneity for Diagnostic and Therapeutic Applications","volume":"20","author":"Carney","year":"2025","journal-title":"Nat. Nanotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e70168","DOI":"10.1002\/jev2.70168","article-title":"Heterogeneity of Extracellular Vesicles and Non-Vesicular Nanoparticles in Glioblastoma","volume":"14","author":"Xu","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e2000118","DOI":"10.1002\/pmic.202000118","article-title":"Understanding Extracellular Vesicle and Nanoparticle Heterogeneity: Novel Methods and Considerations","volume":"21","author":"Phillips","year":"2021","journal-title":"Proteomics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41556-018-0040-4","article-title":"Identification of Distinct Nanoparticles and Subsets of Extracellular Vesicles by Asymmetric Flow Field-Flow Fractionation","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1097\/MOH.0b013e32833e77ee","article-title":"Clinical Relevance of Microparticles from Platelets and Megakaryocytes","volume":"17","author":"Italiano","year":"2010","journal-title":"Curr. Opin. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1182\/blood-2008-06-163832","article-title":"Megakaryocyte-Derived Microparticles: Direct Visualization and Distinction from Platelet-Derived Microparticles","volume":"113","author":"Flaumenhaft","year":"2009","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e70039","DOI":"10.1002\/jev2.70039","article-title":"Comprehensive Phenotyping of Extracellular Vesicles in Plasma of Healthy Humans\u2014Insights Into Cellular Origin and Biological Variation","volume":"14","author":"Holcar","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1111\/jth.15733","article-title":"Beyond the Thrombus: Platelet-Inspired Nanomedicine Approaches in Inflammation, Immune Response, and Cancer","volume":"20","author":"Desai","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dai, Z., Zhao, T., Song, N., Pan, K., Yang, Y., Zhu, X., Chen, P., Zhang, J., and Xia, C. (2022). Platelets and Platelet Extracellular Vesicles in Drug Delivery Therapy: A Review of the Current Status and Future Prospects. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1026386"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","article-title":"The PRIDE Database at 20 Years: 2025 Update","volume":"53","author":"Bandla","year":"2025","journal-title":"Nucleic Acids Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1698\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T05:14:42Z","timestamp":1765084482000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["biom15121698"],"URL":"https:\/\/doi.org\/10.3390\/biom15121698","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]}}}