{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:45:33Z","timestamp":1787726733139,"version":"build-2784847793"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Crossley Barnes Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs), specifically exosomes, carry a cell-type dependent cargo that is transported to the recipient cell and translated in the presence of a required machinery. Differences in the cargo carried by the corneal and conjunctival-derived EVs could be the agent that triggers the transdifferentiation of these two cell populations. Therefore, this study investigates the role of EVs in triggering the plasticity of corneal and conjunctival epithelial cells and identifies prospective miRNA and genes responsible for maintaining ocular surface homeostasis. The EVs were extracted from the conditioned media (after starving) of corneal epithelial (hTCEpi) and conjunctival (HCjE-Gi) cell lines using ultracentrifugation. HCjE-Gi cells were cultured with hTCEpi-derived EVs and vice-versa. The EVs were characterized as exosomes using Nanosight and Flow cytometry. KRT3 and KRT12 were used as associated corneal markers, whereas KRT7 and KRT13 were used as associated conjunctival markers with \u0394Np63 as a differentiation marker. Shift of these markers was an indication of transdifferentiation. The cargo of the extracted exosomes from both the cell types was explored using next-generation sequencing. The hTCEpi-derived EVs induced conjunctival epithelial cells to express the corneal-associated markers KRT3 and KRT12, losing their conjunctival phenotype at both the mRNA and protein level. Simultaneously, HCjE-Gi-derived EVs induced corneal epithelial cells to express the conjunctival associated markers KRT7 and KRT13, losing their corneal phenotype. This process of differentiation was accompanied by an intermediate step of cell de-differentiation showed by up-regulation in the expression of epithelial stem cell marker \u0394Np63, also shown on the ex vivo human cadaveric donor corneas. miRNA molecules (total of 11 including precursor and mature) with significant differences in their relative abundance between the two populations (p &lt; 0.05) were found and investigated. miR-9-5p expression was higher in HCjE-Gi cells and HCjE-Gi-derived EVs when compared to hTCEpi cells and hTCEPi-derived EVs (p &lt; 0.001). The results suggest that EVs released by the two cell types have the ability to influence the transdifferentiation of human conjunctival and corneal epithelial cells. miR-9-5p could have a role in stem cell homeostasis and cell differentiation via HES-1 gene.<\/jats:p>","DOI":"10.3390\/ijms23031718","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:42:33Z","timestamp":1643866953000},"page":"1718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Epithelial Cell-Derived Extracellular Vesicles Trigger the Differentiation of Two Epithelial Cell Lines"],"prefix":"10.3390","volume":"23","author":[{"given":"Tiago","family":"Ramos","sequence":"first","affiliation":[{"name":"Department of Eye and Vision Science, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Institute of Ophthalmology, Faculty of Brain Sciences, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5186-068X","authenticated-orcid":false,"given":"Mohit","family":"Parekh","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, Faculty of Brain Sciences, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Institute of Ophthalmology, Faculty of Brain Sciences, University College London, London EC1V 9EL, UK"},{"name":"St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/229560a0","article-title":"Role of the Pericorneal Papillary Structure in Renewal of Corneal Epithelium","volume":"229","author":"Davanger","year":"1971","journal-title":"Nature"},{"key":"ref_2","first-page":"1533","article-title":"Comparison of limbal and peripheral human corneal epithelium in tissue culture","volume":"29","author":"Ebato","year":"1988","journal-title":"Investig. 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