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To study the molecular mechanisms linking M\u00fcller glia reactivity to progenitor production and neuronal differentiation, we used single-cell RNA sequencing of M\u00fcller glia, progenitors and regenerated progeny from uninjured and light-lesioned retinae. We discover an injury-induced M\u00fcller glia differentiation trajectory that leads into a cell population with a hybrid identity expressing marker genes of M\u00fcller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. We further observe that neurogenic progenitors progressively differentiate to generate retinal ganglion cells first and bipolar cells last, similar to the events observed during retinal development. Our work provides a comprehensive description of M\u00fcller glia and progenitor transcriptional changes and fate decisions in the regenerating retina, which are key to tailor cell differentiation and replacement therapies for retinal dystrophies in humans.<\/jats:p>","DOI":"10.7554\/elife.86507","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T03:51:00Z","timestamp":1681271460000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.86507","source":"Crossref","is-referenced-by-count":37,"title":["Single-cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration"],"prefix":"10.7554","volume":"12","author":[{"given":"Laura","family":"Celotto","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042aqky30","id-type":"ROR","asserted-by":"publisher"}],"name":"Technische Universit\u00e4t Dresden, CRTD - Center for Regenerative Therapies Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Fetscherstra\u00dfe","place":["Dresden, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-2589","authenticated-orcid":true,"given":"Fabian","family":"Rost","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042aqky30","id-type":"ROR","asserted-by":"publisher"}],"name":"Technische Universit\u00e4t Dresden, DRESDEN-Concept Genome Center, Center for Molecular and Cellular Bioengineering (CMCB), Fetscherstra\u00dfe","place":["Dresden, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Machate","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042aqky30","id-type":"ROR","asserted-by":"publisher"}],"name":"Technische Universit\u00e4t Dresden, CRTD - 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