{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:05:12Z","timestamp":1785409512402,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,27]]},"group-title":"Neuroscience","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01NS103758"],"award-info":[{"award-number":["R01NS103758"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01NS128117"],"award-info":[{"award-number":["R01NS128117"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PICT 2017-0389"],"award-info":[{"award-number":["PICT 2017-0389"]}],"id":[{"id":"https:\/\/ror.org\/03stxzb56","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PICT 2018-03713"],"award-info":[{"award-number":["PICT 2018-03713"]}],"id":[{"id":"https:\/\/ror.org\/03stxzb56","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PICT-2020-0046"],"award-info":[{"award-number":["PICT-2020-0046"]}],"id":[{"id":"https:\/\/ror.org\/03stxzb56","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PICT-2021-0077"],"award-info":[{"award-number":["PICT-2021-0077"]}],"id":[{"id":"https:\/\/ror.org\/03stxzb56","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Hippocampal neurogenesis supports learning and memory by generating new granule cells throughout life. However, both the rate and speed of this process decline with age. To elucidate the molecular determinants underlying the effects of aging on neuronal differentiation, we combined lineage tracing of adult-born granule cells (aGCs) with single-nucleus RNA sequencing. This approach produced a temporally resolved transcriptional atlas of aGC development. Aging led to a marked accumulation of postmitotic neuroblasts (NBs), revealing a stage-specific bottleneck in the neurogenic trajectory. Voluntary running reduced NB accumulation by restoring the progression through this developmental impasse, allowing neuronal maturation to be resumed. Notably, this effect involved a significant reduction of apoptosis at the NB stage. Together, these findings identify a reversible apoptotic checkpoint that contributes to age-related neurogenic decline and highlight postmitotic NBs as a key regulatory cell state capable of integrating pro-maturational signals to control the neurogenic output.<\/jats:p>","DOI":"10.64898\/2026.04.23.717949","type":"posted-content","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:36:55Z","timestamp":1777336615000},"source":"Crossref","is-referenced-by-count":0,"title":["Cell-state mapping reveals a reversible neuroblast accumulation in the aging mouse hippocampus"],"prefix":"10.64898","author":[{"given":"Natal\u00ed B.","family":"Rasetto","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magal\u00ed","family":"Herrero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel A.","family":"Berardino","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Integrative Systems Biology, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela J.","family":"Di Bella","sequence":"additional","affiliation":[{"name":"Dept. of Stem Cells and Regenerative Biology, Harvard University & Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiana","family":"Giacomini","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela F.","family":"Trinchero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Arlotta","sequence":"additional","affiliation":[{"name":"Dept. of Stem Cells and Regenerative Biology, Harvard University & Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Chernomoretz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Integrative Systems Biology, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-8348","authenticated-orcid":false,"given":"Alejandro F.","family":"Schinder","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina"},{"name":"Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026043001100583000_2026.04.23.717949v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0260-z"},{"key":"2026043001100583000_2026.04.23.717949v1.2","unstructured":"J. D. A. DG., \u201c\u201cHippocampus\u201d\u201d in The synaptic organization of the brain. (Oxford university press, 2004)."},{"key":"2026043001100583000_2026.04.23.717949v1.3","doi-asserted-by":"crossref","unstructured":"A. F. Schinder , M. F. Trinchero , A. I. Groisman , \u201cSynaptogenesis in the adult CNS\u2014Hippocampus\u201d in Synapse development and maturation. (Elsevier, 2020), pp. 235\u2013253.","DOI":"10.1016\/B978-0-12-823672-7.00010-7"},{"key":"2026043001100583000_2026.04.23.717949v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.021"},{"key":"2026043001100583000_2026.04.23.717949v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.23475"},{"key":"2026043001100583000_2026.04.23.717949v1.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-06-02027.1996"},{"key":"2026043001100583000_2026.04.23.717949v1.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-09-03206.1998"},{"key":"2026043001100583000_2026.04.23.717949v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.12.003"},{"key":"2026043001100583000_2026.04.23.717949v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.064"},{"key":"2026043001100583000_2026.04.23.717949v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.03.010"},{"key":"2026043001100583000_2026.04.23.717949v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.040"},{"key":"2026043001100583000_2026.04.23.717949v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.07.002"},{"key":"2026043001100583000_2026.04.23.717949v1.13","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s43587-023-00370-9","article-title":"Chronic in vivo imaging defines age-dependent alterations of neurogenesis in the mouse hippocampus","volume":"3","year":"2023","journal-title":"Nature Aging"},{"key":"2026043001100583000_2026.04.23.717949v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(03)00083-6"},{"key":"2026043001100583000_2026.04.23.717949v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2006.00243.x"},{"key":"2026043001100583000_2026.04.23.717949v1.16","doi-asserted-by":"publisher","DOI":"10.1159\/000368575"},{"key":"2026043001100583000_2026.04.23.717949v1.17","doi-asserted-by":"crossref","first-page":"739","DOI":"10.3389\/fnins.2019.00739","article-title":"Experience-Dependent Structural Plasticity of Adult-Born Neurons in the Aging Hippocampus","volume":"13","year":"2019","journal-title":"Frontiers in neuroscience"},{"key":"2026043001100583000_2026.04.23.717949v1.18","doi-asserted-by":"crossref","unstructured":"M. F. Trinchero , M. Herrero , A. F. Schinder , Rejuvenating the Brain With Chronic Exercise Through Adult Neurogenesis. (2019).","DOI":"10.3389\/fnins.2019.01000"},{"key":"2026043001100583000_2026.04.23.717949v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/386493a0"},{"key":"2026043001100583000_2026.04.23.717949v1.20","doi-asserted-by":"crossref","unstructured":"C. Vivar , M. C. Potter , H. van Praag , All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis. Neurogenesis and neural plasticity, 189\u2013210 (2013).","DOI":"10.1007\/7854_2012_220"},{"key":"2026043001100583000_2026.04.23.717949v1.21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2174\/156720511797633214","article-title":"Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimer\u2019s disease","volume":"8","year":"2011","journal-title":"Current Alzheimer Research"},{"key":"2026043001100583000_2026.04.23.717949v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22103"},{"key":"2026043001100583000_2026.04.23.717949v1.23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2580-15.2015"},{"key":"2026043001100583000_2026.04.23.717949v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-01971-w"},{"key":"2026043001100583000_2026.04.23.717949v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01848-4"},{"key":"2026043001100583000_2026.04.23.717949v1.26","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp6039"},{"key":"2026043001100583000_2026.04.23.717949v1.27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3178-07.2007"},{"key":"2026043001100583000_2026.04.23.717949v1.28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2345-15.2015"},{"key":"2026043001100583000_2026.04.23.717949v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.07.013"},{"key":"2026043001100583000_2026.04.23.717949v1.30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad7038"},{"key":"2026043001100583000_2026.04.23.717949v1.31","doi-asserted-by":"crossref","unstructured":"H. Hochgerner , A. Zeisel , P. Lonnerberg , S. Linnarsson , Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing. 21, 290\u2013299 (2018).","DOI":"10.1038\/s41593-017-0056-2"},{"key":"2026043001100583000_2026.04.23.717949v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0491-3"},{"key":"2026043001100583000_2026.04.23.717949v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.03.010"},{"key":"2026043001100583000_2026.04.23.717949v1.34","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/stem.2266","article-title":"Heterogeneity of Radial Glia-Like Cells in the Adult Hippocampus","volume":"34","year":"2016","journal-title":"Stem Cells"},{"key":"2026043001100583000_2026.04.23.717949v1.35","doi-asserted-by":"crossref","unstructured":"G. Tosoni et al., Unique transcriptional profiles of adult human immature neurons in healthy aging, Alzheimer\u2019s disease, and cognitive resilience. bioRxiv, 2025.2001. 2008.631686 (2025).","DOI":"10.1101\/2025.01.08.631686"},{"key":"2026043001100583000_2026.04.23.717949v1.36","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2028-6"},{"key":"2026043001100583000_2026.04.23.717949v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature04108"},{"key":"2026043001100583000_2026.04.23.717949v1.38","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00325-13"},{"key":"2026043001100583000_2026.04.23.717949v1.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1380-11.2011"},{"key":"2026043001100583000_2026.04.23.717949v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00745-w"},{"key":"2026043001100583000_2026.04.23.717949v1.41","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01579.x"},{"key":"2026043001100583000_2026.04.23.717949v1.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0202-11.2011"},{"key":"2026043001100583000_2026.04.23.717949v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.03.018"},{"key":"2026043001100583000_2026.04.23.717949v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00759-4"},{"key":"2026043001100583000_2026.04.23.717949v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.09.026"},{"key":"2026043001100583000_2026.04.23.717949v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.01.003"},{"key":"2026043001100583000_2026.04.23.717949v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.08.014"},{"key":"2026043001100583000_2026.04.23.717949v1.48","doi-asserted-by":"crossref","unstructured":"M. F. Trinchero , et al., Audiovisual gamma stimulation enhances hippocampal neurogenesis and neural circuit plasticity in aging mice. bioRxiv (2025).","DOI":"10.1101\/2025.01.13.632794"},{"key":"2026043001100583000_2026.04.23.717949v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.018"},{"key":"2026043001100583000_2026.04.23.717949v1.50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018472"},{"key":"2026043001100583000_2026.04.23.717949v1.51","doi-asserted-by":"crossref","unstructured":"H. Hagihara , K. Toyama , N. Yamasaki , T. Miyakawa , Dissection of hippocampal dentate gyrus from adult mouse. Journal of visualized experiments: JoVE, 1543 (2009).","DOI":"10.3791\/1543-v"},{"key":"2026043001100583000_2026.04.23.717949v1.52","unstructured":"G. Paxinos , K. B. J. Franklin , The mouse brain in stereotaxic coordinates. (2001)."},{"key":"2026043001100583000_2026.04.23.717949v1.53","doi-asserted-by":"crossref","first-page":"979","DOI":"10.12688\/f1000research.73600.2","article-title":"Doublet identification in single-cell sequencing data using scDblFinder","volume":"10","year":"2022","journal-title":"f1000research"},{"key":"2026043001100583000_2026.04.23.717949v1.54","first-page":"2122","article-title":"A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor","volume":"5","year":"2016","journal-title":"F1000Research"},{"key":"2026043001100583000_2026.04.23.717949v1.55","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41592-019-0654-x","article-title":"Orchestrating single-cell analysis with Bioconductor","volume":"17","year":"2020","journal-title":"Nature methods"},{"key":"2026043001100583000_2026.04.23.717949v1.56","doi-asserted-by":"crossref","unstructured":"K. Street et al., Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC genomics 19, 477 (2018).","DOI":"10.1186\/s12864-018-4772-0"},{"key":"2026043001100583000_2026.04.23.717949v1.57","doi-asserted-by":"crossref","unstructured":"M. Bastian , S. Heymann , M. Jacomy (2009) Gephi: an open source software for exploring and manipulating networks. in Proceedings of the international AAAI conference on web and social media, pp 361\u2013362.","DOI":"10.1609\/icwsm.v3i1.13937"},{"key":"2026043001100583000_2026.04.23.717949v1.58","doi-asserted-by":"crossref","first-page":"vbae062","DOI":"10.1093\/bioadv\/vbae062","article-title":"scX: a user-friendly tool for scRNAseq exploration","volume":"4","year":"2024","journal-title":"Bioinformatics Advances"},{"key":"2026043001100583000_2026.04.23.717949v1.59","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTZ931"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.23.717949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:10:28Z","timestamp":1777536628000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.23.717949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":59,"URL":"https:\/\/doi.org\/10.64898\/2026.04.23.717949","relation":{},"subject":[],"published":{"date-parts":[[2026,4,27]]},"subtype":"preprint"}}