{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:32:59Z","timestamp":1789659179394,"version":"4.0.1"},"reference-count":84,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council, University Grants Committee","award":["11103819"],"award-info":[{"award-number":["11103819"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"crossref"}]},{"award":["11103819"],"award-info":[{"award-number":["11103819"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research Grants Council, University Grants Committee","award":["11102922"],"award-info":[{"award-number":["11102922"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"crossref"}]},{"award":["11102922"],"award-info":[{"award-number":["11102922"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research Grants Council, University Grants Committee","award":["11100723"],"award-info":[{"award-number":["11100723"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"crossref"}]},{"award":["11100723"],"award-info":[{"award-number":["11100723"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Health and Medical Research Fund","award":["05160276"],"award-info":[{"award-number":["05160276"]}]},{"name":"Health and Medical Research Fund","award":["06172466"],"award-info":[{"award-number":["06172466"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    In regenerative species, such as teleost fish, M\u00fcller glia (MG) autonomously re-enter the cell cycle after injury and give rise to functional retinal neurons. In contrast, the loss of retinal neurons in mammals is irreversible due to the limited proliferative and regenerative ability of MG. Various strategies have been developed to induce proliferation of mature mouse MG with or without injury, yet most MG daughter cells retain glial cell fate. Here, we found that MG progenies maintain high Notch signaling, which may constrain their neurogenic potential. Conditional deletion of\n                    <jats:italic>Rbpj<\/jats:italic>\n                    , the central transcriptional effector of Notch, induced limited MG-to-neuron conversion in mature MG without proliferation. However,\n                    <jats:italic>Rbpj<\/jats:italic>\n                    deletion, combined with forced MG proliferation by overexpressing\n                    <jats:italic>Ccnd1<\/jats:italic>\n                    and suppressing\n                    <jats:italic>Cdkn1b<\/jats:italic>\n                    , significantly promoted MG dedifferentiation and ectopic expression of the neuronal marker Otx2 in MG daughter cells in uninjured mouse retina. Combining Notch inhibition with MG cell cycle re-activation not only increased the numbers of bipolar- and amacrine-like cells generated from MG but also promoted the further differentiation toward ON-cone, OFF-cone, and rod-bipolar subtypes. Single-nucleus RNA and ATAC sequencing data revealed that Notch inhibition facilitated the formation of MG-derived progenitor-like cells while MG proliferation increased chromatin accessibility of neurogenic genes. Notably, most MG-derived cells survived long term despite incomplete maturation. Together, our findings delineate how Notch inhibition and MG proliferation, alone or in combination, influence the regenerative potential of MG in the mammalian retina.\n                  <\/jats:p>","DOI":"10.7554\/elife.111251","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:30:18Z","timestamp":1777386618000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.111251","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic inhibition of Notch signaling and forced cell cycle re-entry drive M\u00fcller glia reprogramming in uninjured mouse retina"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6599-624X","authenticated-orcid":true,"given":"Baoshan","family":"Liao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03q8dnn23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong","place":["Hong Kong, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0971-2851","authenticated-orcid":true,"given":"Chengshang","family":"Lyu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03q8dnn23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong","place":["Hong Kong, 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