{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:50:30Z","timestamp":1782280230744,"version":"3.54.5"},"posted":{"date-parts":[[2025,5,2]]},"group-title":"Neuroscience","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01EY036173"],"award-info":[{"award-number":["R01EY036173"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The vertebrate retina serves as a model for studying neurogenesis and cell fate specification, with retinal progenitor cells following a tightly regulated temporal sequence to generate distinct cell types. Meis1 and Meis2 are transcription factors implicated in early retinal development, but their role in late-stage RPCs remains poorly understood. Here, we investigate whether\n                  <jats:italic>Meis1<\/jats:italic>\n                  and\n                  <jats:italic>Meis2<\/jats:italic>\n                  overexpression in postnatal mouse RPCs can alter temporal identity and induce early-born cell types. Using electroporation and single-cell RNA sequencing, we find that while these factors modestly upregulate early-stage gene regulatory network components, they do not repress late-stage transcription factors or induce early-born retinal cells.\n                  <jats:italic>Meis1<\/jats:italic>\n                  overexpression reduces proliferation and inhibits neurogenesis, whereas\n                  <jats:italic>Meis2<\/jats:italic>\n                  overexpression accelerates neurogenic progression without altering fate commitment. Our findings suggest that overexpression of\n                  <jats:italic>Meis1<\/jats:italic>\n                  and\n                  <jats:italic>Meis2<\/jats:italic>\n                  modulate largely non-overlapping aspects of temporal identity and neurogenic competence but are insufficient to fully reprogram late-stage progenitors. These results have implications for regenerative strategies aimed at reprogramming retinal cells for therapeutic purposes.\n                <\/jats:p>","DOI":"10.1101\/2025.05.01.651492","type":"posted-content","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:54:27Z","timestamp":1746172467000},"source":"Crossref","is-referenced-by-count":4,"title":["Overexpression of Meis factors in late-stage retinal progenitors yields complex effects on temporal patterning and neurogenesis"],"prefix":"10.64898","author":[{"given":"Patrick","family":"Leavey","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Pannullo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-8476","authenticated-orcid":false,"given":"Seth","family":"Blackshaw","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041206340397000_2025.05.01.651492v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"2026041206340397000_2025.05.01.651492v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2122168120"},{"key":"2026041206340397000_2025.05.01.651492v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21458"},{"key":"2026041206340397000_2025.05.01.651492v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"2026041206340397000_2025.05.01.651492v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00756-6"},{"key":"2026041206340397000_2025.05.01.651492v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3767"},{"key":"2026041206340397000_2025.05.01.651492v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2019.04.010"},{"key":"2026041206340397000_2025.05.01.651492v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2013136118"},{"key":"2026041206340397000_2025.05.01.651492v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-5-22"},{"key":"2026041206340397000_2025.05.01.651492v1.10","doi-asserted-by":"publisher","DOI":"10.1242\/dev.059683"},{"key":"2026041206340397000_2025.05.01.651492v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-023-01767-Y"},{"key":"2026041206340397000_2025.05.01.651492v1.12","doi-asserted-by":"publisher","DOI":"10.1242\/dev.012088"},{"key":"2026041206340397000_2025.05.01.651492v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8598"},{"key":"2026041206340397000_2025.05.01.651492v1.14","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20132279"},{"key":"2026041206340397000_2025.05.01.651492v1.15","unstructured":"Kolde, Raivo . 2012. \u201cPheatmap: Pretty Heatmaps.\u201d R Package Version 1 (2)."},{"key":"2026041206340397000_2025.05.01.651492v1.16","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.18.613666"},{"key":"2026041206340397000_2025.05.01.651492v1.17","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn2091"},{"key":"2026041206340397000_2025.05.01.651492v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.04.009"},{"key":"2026041206340397000_2025.05.01.651492v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109994"},{"key":"2026041206340397000_2025.05.01.651492v1.20","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122176"},{"key":"2026041206340397000_2025.05.01.651492v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2014.12.052"},{"key":"2026041206340397000_2025.05.01.651492v1.22","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.044883"},{"key":"2026041206340397000_2025.05.01.651492v1.23","unstructured":"\u201c[No Title].\u201d n.d. 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