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Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cell-based therapies hold great promise for treating late-stage retinal degenerative diseases. However, photoreceptor cell transplantation has been limited by poor cellular integration, suggesting that an ideal population of donor cells has not yet been defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we utilized single-cell RNA-sequencing and lineage tracing to assess the heterogeneity of photoreceptor precursor cells during murine retinal development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Subgroup analysis revealed three transcriptionally distinct populations of\n                      <jats:italic>Crx<\/jats:italic>\n                      + cells from postnatal day 2\u20136 retinas which are consistent with early (\n                      <jats:italic>Dll1<\/jats:italic>\n                      +), intermediate (\n                      <jats:italic>Neurod4<\/jats:italic>\n                      +), and late (\n                      <jats:italic>Prom1<\/jats:italic>\n                      +) photoreceptor precursor cells. Lineage tracing with subpopulation-enriched Cre mice showed that\n                      <jats:italic>Dll1<\/jats:italic>\n                      +,\n                      <jats:italic>Neurod4<\/jats:italic>\n                      +, and\n                      <jats:italic>Prom1<\/jats:italic>\n                      + cells all generate photoreceptor cells, and captured dynamic changes in gene expression suggestive of sequential states of photoreceptor differentiation. Transcriptomic analysis revealed that similar\n                      <jats:italic>CRX<\/jats:italic>\n                      + subpopulations are present in maturing human retinal organoids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the heterogeneity of neonatal photoreceptor precursor cells, and could help inform future strategies to isolate an optimal population of cells for retinal regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1814134","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:57:28Z","timestamp":1780577848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lineage tracing reveals photoreceptor precursor cell subpopulations that contribute to murine retinogenesis"],"prefix":"10.3389","volume":"14","author":[{"given":"Joseph J.","family":"Yano","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna J.","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaidi T.","family":"Barati-Stec","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E.","family":"Uyhazi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.gep.2017.03.001","article-title":"Temporal profiling of photoreceptor lineage gene expression during murine retinal development","author":"Aavani","year":"2017","journal-title":"Gene Expr. 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