{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:11Z","timestamp":1785427271466,"version":"3.56.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    Gliomas are characterized by poor survival rate and limited options for treatment. Based on the transcriptional enrichment for oligodendrocyte progenitor cell (OPC) transcripts, the proneural glioma is thought to arise from transformation of OPCs. Here, we injected mutant BB-p53n OPCs (with\n                    <jats:italic>Trp53<\/jats:italic>\n                    deletion and PDGF-BB overexpression) into recipient mice and performed single-nucleus RNA sequencing (snRNA-seq) of the injected cells and of brain tissue at early and late time points after injection, coincident with neuroimaging detection of tumoral masses. Analysis of tumor-bearing brain samples, identified a cluster that was not detected in the normal brain, but was enriched for OPC markers (\n                    <jats:italic>Olig2),<\/jats:italic>\n                    cell cycle genes (\n                    <jats:italic>Myc<\/jats:italic>\n                    ) and glioma markers (\n                    <jats:italic>Top2a, Sox2<\/jats:italic>\n                    ), which we named \u201cOPC-like.\u201d The clusters with \u201cOPC-like\u201d signature, were also the ones with greater genomic distribution of inferred copy number variations (inferCNVs) and high proliferative rate, and were therefore denoted as \u201ctumors.\u201d The inferCNV genomic load was higher in late-stage samples compared to early ones, indicative of progressive genomic instability. Immunohistochemical analysis validated the high proliferative rate and widespread expression of the \u201cOPC-like\u201d markers TOP2A and SOX2. Pseudotime analysis of cycling cells identified a trajectory of decreasing cell cycle checkpoint regulation and increasing synaptic signaling from early to late timepoints. Thus, the early timepoints were characterized by the emergence of highly proliferative cell clusters with a unique \u201cOPC-like\u201d transcriptional signature and inferCNVs, and the late timepoints were characterized by further genomic spreading of inferCNVs, loss of cell cycle checkpoints and transcriptional changes consistent with increased neuron-glioma interactions\n                  <\/jats:p>","DOI":"10.3389\/fncel.2026.1713437","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T23:10:17Z","timestamp":1782774617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-nucleus transcriptomics identifies cell cycle and synaptic pathway dysregulation during OPC-to-glioma progression"],"prefix":"10.3389","volume":"20","author":[{"given":"Dennis","family":"Huang","sequence":"first","affiliation":[{"name":"Program in Molecular, Cellular and Developmental Biology at The Graduate Center of The City University of New","place":["New York, NY, United States"]},{"name":"Neuroscience Initiative, Advance Science Research Center, Graduate Center of The City University of New York","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Mela","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Neuroscience Initiative, Advance Science Research Center, Graduate Center of The City University of New York","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Canoll","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Casaccia","sequence":"additional","affiliation":[{"name":"Program in Molecular, Cellular and Developmental Biology at The Graduate Center of The City University of New","place":["New York, NY, United States"]},{"name":"Neuroscience Initiative, Advance Science Research Center, Graduate Center of The City University of New York","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e26740","DOI":"10.1371\/journal.pone.0026740","article-title":"Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas","volume":"6","author":"Alonso","year":"2011","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. 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