{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T08:09:57Z","timestamp":1793866197917,"version":"4.6.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012020","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000}}],"reference-count":114,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"crossref","award":["RGPIN-2017-03649 and RGPIN-2024-04345"],"award-info":[{"award-number":["RGPIN-2017-03649 and RGPIN-2024-04345"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-142338"],"award-info":[{"award-number":["MOP-142338"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-180243"],"award-info":[{"award-number":["PJT-180243"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT \u2013 400973"],"award-info":[{"award-number":["PJT \u2013 400973"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-165973"],"award-info":[{"award-number":["MOP-165973"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U of Calgary Eyes High Fellowship"},{"name":"University of Toronto Department of Laboratory Medicine and Pathobiology"},{"name":"CIHR Frederick Banting and Charles Best Masters"},{"name":"University of Toronto Vision Science Research Program"},{"name":"Canada Graduate Scholarship"},{"name":"VSRP Scholarship"},{"name":"Ontario Graduate Scholarship"},{"name":"R.O. Torrance Bursary"},{"name":"Natural Sciences and Engineering Research Council (NSERC) of Canada"},{"name":"ACHRI\/CIHR Training Grant at the University of Calgary"},{"name":"University of Toronto Department of Biochemistry Undergraduate Research Opportunity Program"},{"name":"Alberta Innovates Health Solution"},{"name":"CIHR Canada Hope Fellowship"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    M\u00fcller glia arise from late-stage retinal progenitor cells (RPCs) as a distinct lineage that diverges from neurogenic trajectories. Here, we identify the maternally imprinted gene\n                    <jats:italic>Plagl1<\/jats:italic>\n                    as a key transcriptional regulator of gliogenesis in the murine retina.\n                    <jats:italic>Plagl1<\/jats:italic>\n                    is expressed during the RPC-to-glia transition and is dynamically regulated in M\u00fcller glia following injury. To define its developmental role, we analyzed\n                    <jats:italic>Plagl1<\/jats:italic>\n                    <jats:sup>\u207a\/\u207bpat<\/jats:sup>\n                    null mutant retinas at postnatal day 7 (P7), when central retinal gliogenesis is complete. In the absence of\n                    <jats:italic>Plagl1<\/jats:italic>\n                    , Sox9\u2009\u207a\u2009glial\/precursor cells were displaced and proliferated ectopically, with structural dysmorphologies, reactive gliosis, and impaired visual processing persisting into later postnatal stages. Bulk RNA-seq and ATAC-seq revealed widespread reductions in chromatin accessibility and transcriptional dysregulation affecting epigenetic modifiers, translational machinery, fate-specifying transcription factors, cell cycle regulators, and signaling pathways. Single-cell pseudobulk analysis showed that\n                    <jats:italic>Plagl1<\/jats:italic>\n                    loss disrupts chromatin, transcriptional, and translational programs specifically within Sox9\u2009\u207a\u2009cells, encompassing M\u00fcller glia and precursor populations, pinpointing these cells as the source of defects in\n                    <jats:italic>Plagl1<\/jats:italic>\n                    <jats:sup>\u207a\/\u207bpat<\/jats:sup>\n                    retinas. Notch signaling was elevated in\n                    <jats:italic>Plagl1<\/jats:italic>\n                    -deficient glia, and genetic activation at P14 displaced Sox9\u2009\u207a\u2009glial cells, without inducing proliferation. Similarly, conditional deletion of\n                    <jats:italic>Plagl1<\/jats:italic>\n                    in postnatal M\u00fcller glia at P14 disrupted positioning and not cell cycle exit, confirming a cell-autonomous requirement for M\u00fcller glia positioning that is independent of proliferation control. Since these conditional manipulations could only be performed at P14 at the earliest, they reveal\n                    <jats:italic>Plagl1<\/jats:italic>\n                    \u2019s later functions in postmitotic glia and complement, rather than mirror, the earlier P7 mixed RPC\/glial null phenotype. Together these findings establish\n                    <jats:italic>Plagl1<\/jats:italic>\n                    as a critical regulator of the late-stage RPC to M\u00fcller glia transition, acting through coordinated control of chromatin accessibility and gene expression programs to ensure timely cell cycle exit. This function aligns with\n                    <jats:italic>Plagl1<\/jats:italic>\n                    \u2019s broader tumor suppressor role in stabilizing postmitotic, differentiated cell states across tissues.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012020","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:42:02Z","timestamp":1773855722000},"page":"e1012020","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Plagl1 regulates the retinal progenitor cell to M\u00fcller glial cell transition"],"prefix":"10.1371","volume":"22","author":[{"given":"Yacine","family":"Touahri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4981-1950","authenticated-orcid":true,"given":"Alissa","family":"Pak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke Ajay","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6456-0860","authenticated-orcid":true,"given":"Hedy","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Belfiore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslav","family":"Ilnytskyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"van Oosten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-6915","authenticated-orcid":true,"given":"Lata","family":"Adnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Dixit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Zinyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia 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