{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:03:28Z","timestamp":1793721808796,"version":"4.6.1"},"posted":{"date-parts":[[2026,9,14]]},"group-title":"Genomics","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Alternative splicing greatly expands the diversity of gene products encoded by the human genome. Single-cell transcriptomic atlases have characterized human cell types through gene-level expression, but short-read sequencing has limited the ability to resolve full-length isoforms and their functional consequences. Here, we present a cross-tissue single-cell long-read isoform atlas spanning 26 human tissues. We identify hundreds of thousands of novel isoforms along with their cell-type-specific usage, and discover that over one-third of expressed isoforms are absent from existing reference databases. We further demonstrate that isoform usage is a structured, measurable axis of cellular identity that is distinct from gene expression. Applying this framework to cellular senescence, we resolve p16\n                  <jats:sup>INK4a<\/jats:sup>\n                  and p14\n                  <jats:sup>ARF<\/jats:sup>\n                  transcripts from the\n                  <jats:italic>CDKN2A<\/jats:italic>\n                  locus in individual cells and uncover cell-type-dependent isoform remodeling associated with the p16\n                  <jats:sup>INK4a<\/jats:sup>\n                  senescence program. This isoform-resolved single-cell atlas offers a versatile framework to dissect the cellular logic of isoform regulation in senescence and beyond.\n                <\/jats:p>","DOI":"10.64898\/2026.09.11.748700","type":"posted-content","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:40:12Z","timestamp":1789432812000},"source":"Crossref","is-referenced-by-count":1,"title":["Single-cell splice isoform usage reveals distinct axes of cellular identity and senescence"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9844-7852","authenticated-orcid":false,"given":"Madhav","family":"Mantri","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Stanford University; Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Detweiler","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University; Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie Ha-Young","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University; Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University; Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department 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