{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:13:22Z","timestamp":1784891602721,"version":"3.55.0"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007214","name":"Velux Stiftung","doi-asserted-by":"publisher","award":["1852"],"award-info":[{"award-number":["1852"]}],"id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"conahcyt","doi-asserted-by":"crossref","award":["A1-S-25777"],"award-info":[{"award-number":["A1-S-25777"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The regenerative response of retinal cells to injury and aging depends on the epigenomic plasticity that enables the dedifferentiation and neuronal differentiation capacities of M\u00fcller glial cells (MG). In mammals, this regenerative ability is extremely limited, and disruptions in epigenetic mechanisms, particularly those involving DNA methylation and demethylation, may underlie this restricted potential. To explore this possibility, we aimed to develop DNA methylation-targeting molecular tools to enhance the dedifferentiation and neurogenic capacity of primary MG cultures derived from mouse retina. Using CRISPR\/dCas9-based gene regulation technology, we selectively and transiently inhibited\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    , a de novo DNA methyltransferase previously implicated in maintaining transcriptional repression, for approximately 3\u20135 days. Our results show that\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    knockdown leads to sustained upregulation of pluripotency-associated genes, including\n                    <jats:italic>Ascl1<\/jats:italic>\n                    ,\n                    <jats:italic>Lin28<\/jats:italic>\n                    , and\n                    <jats:italic>Nestin<\/jats:italic>\n                    , as measured by RT-qPCR and immunofluorescence. This epigenetic modulation also promoted increased cell proliferation and migration, both hallmarks of a regenerative response. Furthermore,\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    knockdown, either alone or in combination with neurogenic stimuli, induced MG to acquire neuronal-like morphologies and express the early neuronal marker \u03b2III-tubulin. These findings suggest that\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    acts as a repressive regulator of MG plasticity, likely serving as an epigenetic barrier that counteracts injury-induced demethylation events. Overall, our study identifies\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    as a critical modulator of MG fate and highlights the potential of its targeted downregulation to facilitate reprogramming. By prolonging the transient progenitor-like state of MG, DNMT3a inhibition may serve as a complementary approach to unlock the neurogenic and regenerative potential of the mammalian retina, offering promising avenues for future therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0337891","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:26:26Z","timestamp":1765995986000},"page":"e0337891","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted knockdown of DNA methyltransferase 3a (DNMT3a) unlocks dedifferentiation and neurogenic potential in mouse retinal M\u00fcller glia"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6416-6848","authenticated-orcid":true,"given":"Rebeca","family":"Victoria-Chavez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0297-4218","authenticated-orcid":true,"given":"Monica","family":"Lamas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"issue":"7","key":"pone.0337891.ref001","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nrn3723","article-title":"M\u00fcller glial cell reprogramming and retina regeneration","volume":"15","author":"D Goldman","year":"2014","journal-title":"Nat Rev Neurosci"},{"key":"pone.0337891.ref002","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1146\/annurev-vision-121219-081808","article-title":"Reprogramming m\u00fcller glia to 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