{"publisher":"American Association for the Advancement of Science","issue":"6","status":"public","date_updated":"2026-03-02T14:23:22Z","has_accepted_license":"1","volume":12,"scopus_import":"1","day":"01","OA_place":"publisher","oa":1,"type":"journal_article","license":"https://creativecommons.org/licenses/by-nc/4.0/","intvolume":"        12","department":[{"_id":"CaHe"}],"quality_controlled":"1","month":"02","oa_version":"Published Version","article_processing_charge":"Yes","author":[{"first_name":"Vidyanand","full_name":"Sasidharan, Vidyanand","last_name":"Sasidharan"},{"last_name":"Ancellotti","full_name":"Ancellotti, Laura","first_name":"Laura"},{"full_name":"Doddihal, Viraj","first_name":"Viraj","last_name":"Doddihal","id":"034e0824-174b-11ef-b32b-9366a0e70d1c"},{"last_name":"Brewster","first_name":"Carolyn","full_name":"Brewster, Carolyn"},{"last_name":"Mann","first_name":"Frederick","full_name":"Mann, Frederick"},{"last_name":"McKinney","first_name":"Mary Cathleen","full_name":"McKinney, Mary Cathleen"},{"first_name":"Joseph","full_name":"Varberg, Joseph","last_name":"Varberg"},{"last_name":"Ross","first_name":"Eric","full_name":"Ross, Eric"},{"last_name":"Deng","first_name":"Fengyan","full_name":"Deng, Fengyan"},{"last_name":"Yi","first_name":"Kexi","full_name":"Yi, Kexi"},{"last_name":"Sánchez Alvarado","first_name":"Alejandro","full_name":"Sánchez Alvarado, Alejandro"}],"article_type":"original","title":"Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians","date_published":"2026-02-01T00:00:00Z","article_number":"eady1461","abstract":[{"lang":"eng","text":"Planarian flatworms are known for their remarkable regenerative capacity; however, the precise intercellular communication mechanisms underlying this process remain unsolved. Here, we report the discovery and characterization of abundant extracellular vesicles (EVs) in planarians. Using imaging and molecular analysis, we show conservation of biogenesis, morphology, and protein composition of planarian EVs. Environmental stressors significantly elevate EV release, indicating that planarians dynamically regulate vesicle production. Functionally, planarian EVs mediate intercellular communication by transferring regulatory signals: We find that they shuttle small RNAs that effect systemic RNA interference (RNAi) throughout the organism. Notably, gene knockdown experiments reveal a crucial role for AGO-3, a member of the Argonaute family of proteins, in modulating the association of small interfering RNAs with EVs, linking the intracellular RNAi machinery to EV-based signaling. These findings highlight EVs as pivotal mediators of cell-cell communication in planarians, with broad implications for understanding the coordination of gene regulation and tissue regeneration in animals."}],"DOAJ_listed":"1","citation":{"chicago":"Sasidharan, Vidyanand, Laura Ancellotti, Viraj Doddihal, Carolyn Brewster, Frederick Mann, Mary Cathleen McKinney, Joseph Varberg, et al. “Extracellular Vesicles Mediate Stem Cell Signaling and Systemic RNAi in Planarians.” <i>Science Advances</i>. American Association for the Advancement of Science, 2026. <a href=\"https://doi.org/10.1126/sciadv.ady1461\">https://doi.org/10.1126/sciadv.ady1461</a>.","ista":"Sasidharan V, Ancellotti L, Doddihal V, Brewster C, Mann F, McKinney MC, Varberg J, Ross E, Deng F, Yi K, Sánchez Alvarado A. 2026. Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians. Science Advances. 12(6), eady1461.","mla":"Sasidharan, Vidyanand, et al. “Extracellular Vesicles Mediate Stem Cell Signaling and Systemic RNAi in Planarians.” <i>Science Advances</i>, vol. 12, no. 6, eady1461, American Association for the Advancement of Science, 2026, doi:<a href=\"https://doi.org/10.1126/sciadv.ady1461\">10.1126/sciadv.ady1461</a>.","ieee":"V. Sasidharan <i>et al.</i>, “Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians,” <i>Science Advances</i>, vol. 12, no. 6. American Association for the Advancement of Science, 2026.","ama":"Sasidharan V, Ancellotti L, Doddihal V, et al. Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians. <i>Science Advances</i>. 2026;12(6). doi:<a href=\"https://doi.org/10.1126/sciadv.ady1461\">10.1126/sciadv.ady1461</a>","short":"V. Sasidharan, L. Ancellotti, V. Doddihal, C. Brewster, F. Mann, M.C. McKinney, J. Varberg, E. Ross, F. Deng, K. Yi, A. Sánchez Alvarado, Science Advances 12 (2026).","apa":"Sasidharan, V., Ancellotti, L., Doddihal, V., Brewster, C., Mann, F., McKinney, M. C., … Sánchez Alvarado, A. (2026). Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.ady1461\">https://doi.org/10.1126/sciadv.ady1461</a>"},"file_date_updated":"2026-03-02T14:19:35Z","ddc":["570"],"OA_type":"gold","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["2375-2548"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"year":"2026","language":[{"iso":"eng"}],"acknowledgement":"We thank all the Sánchez Alvarado lab members for inputs and discussions. We are grateful to the Stowers Aquatics (particularly the Planarian team), Microscopy, and Molecular Biology core facilities for technical contributions and method development; e. n. lissek and A. Fujii from Oni US and S. Wang from the University of Missouri, Kansas city, for assistance with dStORM imaging; and d. Alburty and A. Page from innovaprep for assisting with the ntA. We also thank M. Miller for the illustrations. This work was supported by the hhMi and Stowers institute. ","doi":"10.1126/sciadv.ady1461","publication":"Science Advances","date_created":"2026-03-02T10:08:07Z","file":[{"success":1,"checksum":"fa9f6dafe3538e2d2872c098e06d1712","date_created":"2026-03-02T14:19:35Z","content_type":"application/pdf","date_updated":"2026-03-02T14:19:35Z","file_name":"2026_ScienceAdv_Sasidharan.pdf","relation":"main_file","file_id":"21389","file_size":2841345,"creator":"dernst","access_level":"open_access"}],"_id":"21383"}