{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:05:03Z","timestamp":1789617903999,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,13]]},"group-title":"Cell Biology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,13]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Adult central nervous systems (CNS) are generally constrained by limited cellular replacement. How regenerating organisms integrate structural maintenance with continuous, cyclic renewal remains unresolved. Here, we leverage the colonial chordate\n                  <jats:italic>Botryllus schlosseri<\/jats:italic>\n                  which completely resorbs and regenerates its entire CNS\n                  <jats:italic>de novo<\/jats:italic>\n                  weekly. FACS, Combining indexed single-cell sorting, Smart-seq3 sequencing, spatial mapping, and temporal deconvolution, our studies suggest that this continuous CNS renewal is mediated by an intrinsic pool of lineage-restricted neural stem cells. Single-cell analysis resolved a conserved\n                  <jats:italic>SOX2<\/jats:italic>\n                  \/\n                  <jats:italic>NOTCH1<\/jats:italic>\n                  \/\n                  <jats:italic>NEUROG1<\/jats:italic>\n                  prospective progenitor continuum alongside mature excitability-defined neurons. Brain aging drives a phase-specific desynchronization of this regenerative program, inducing early hyper-activation followed by a sudden collapse. Finally, syngeneic transplantation and\n                  <jats:italic>in vivo<\/jats:italic>\n                  tracking show that neural-complex-derived cells persist after vascular delivery and localize to developing bud and neural-associated territories, with injury-associated accumulation near the neural gland. This work establishes a spatiotemporal framework for lifelong chordate CNS renewal and aging.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>Smart-seq3 atlas resolves 6 cell states in the regenerating chordate brain<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Conserved\n                        <jats:italic>SOX2<\/jats:italic>\n                        <jats:sup>+<\/jats:sup>\n                        \/\n                        <jats:italic>NOTCH1<\/jats:italic>\n                        <jats:sup>+<\/jats:sup>\n                        \/\n                        <jats:italic>NEURO1<\/jats:italic>\n                        <jats:sup>+<\/jats:sup>\n                        continuum drives adult neurogenesis.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Neural-complex small cells home to bud niches and integrate upon turnover<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Brain aging stems from ancestral stem-cell exhaustion across cyclic renewal<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>In Brief<\/jats:title>\n                  <jats:p>\n                    Anselmi et al. establish a spatiotemporal single-cell atlas of the cyclically regenerating\n                    <jats:italic>Botryllus schlosseri<\/jats:italic>\n                    central nervous system, identifying a conserved\n                    <jats:italic>SOX2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    \/\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    \/\n                    <jats:italic>NEURO1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    neural progenitor continuum. Transplanted neural-complex-derived cells persist in vivo and localize to developing bud and neural-associated territories, while lifelong brain aging is driven by the cumulative exhaustion of this ancestral stem cell pool.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.11.750342","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T14:40:12Z","timestamp":1789310412000},"source":"Crossref","is-referenced-by-count":0,"title":["Lifelong Invertebrate Chordate Central Nervous System Regeneration is Driven by a Migrating Pool of Conserved Neural Stem Cells program"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-1133","authenticated-orcid":false,"given":"Chiara","family":"Anselmi","sequence":"first","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Biology Department, Hopkins Marine 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