{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:02:30Z","timestamp":1778860950868,"version":"3.51.4"},"reference-count":64,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder caused by mutations within nibrin (NBN), a DNA damage repair protein. Hallmarks of NBS include chromosomal instability and clinical manifestations such as growth retardation, immunodeficiency, and progressive microcephaly. We employed induced pluripotent stem cell-derived cerebral organoids from two NBS patients to study the etiology of microcephaly. We show that NBS organoids carrying the homozygous 657del5 NBN mutation are significantly smaller with disrupted cyto-architecture. The organoids exhibit premature differentiation, and Neuronatin (NNAT) over-expression. Furthermore, pathways related to DNA damage response and cell cycle are differentially regulated compared to controls. After exposure to bleomycin, NBS organoids undergo delayed p53-mediated DNA damage response and aberrant trans-synaptic signaling, which ultimately leads to neuronal apoptosis. Our data provide insights into how mutations within NBN alters neurogenesis in NBS patients, thus providing a proof of concept that cerebral organoids are a valuable tool for studying DNA damage-related disorders.<\/jats:p>","DOI":"10.3390\/cells11050802","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:00:40Z","timestamp":1645783240000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Impaired p53-Mediated DNA Damage Response Contributes to Microcephaly in Nijmegen Breakage Syndrome Patient-Derived Cerebral Organoids"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-6539","authenticated-orcid":false,"given":"Soraia","family":"Martins","sequence":"first","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-9728","authenticated-orcid":false,"given":"Lars","family":"Erichsen","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5022-8087","authenticated-orcid":false,"given":"Angeliki","family":"Datsi","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-7051","authenticated-orcid":false,"given":"Wasco","family":"Wruck","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Goering","sequence":"additional","affiliation":[{"name":"Institute for Pathology, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleftheria","family":"Chatzantonaki","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa Cristina Meira","family":"de Amorim","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Rossi","sequence":"additional","affiliation":[{"name":"IUF-Leibniz Research Institute for Environmental Medicine, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystyna H.","family":"Chrzanowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-6761","authenticated-orcid":false,"given":"James","family":"Adjaye","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.dnarep.2008.03.005","article-title":"The role of the DNA damage response in neuronal development, organization and maintenance","volume":"7","author":"Barzilai","year":"2008","journal-title":"DNA Repair"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1111\/j.1471-4159.2006.03907.x","article-title":"Oxidative stress and neurodegeneration: Where are we now?","volume":"97","author":"Halliwell","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1750-1172-7-13","article-title":"Nijmegen breakage syndrome (NBS)","volume":"7","author":"Chrzanowska","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","unstructured":"Varon, R., Demuth, I., and Chrzanowska, K.H. (1993). Nijmegen Breakage Syndrome, University of Washington."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.dnarep.2004.03.004","article-title":"Nijmegen breakage syndrome: Clinical manifestation of defective response to DNA double-strand breaks","volume":"3","author":"Digweed","year":"2004","journal-title":"DNA Repair"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E3","DOI":"10.1136\/jmg.38.1.e3","article-title":"Atypical clinical picture of the Nijmegen breakage syndrome associated with developmental abnormalities of the brain","volume":"38","author":"Chrzanowska","year":"2001","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1093\/jnci\/djm251","article-title":"Cancer Risk of Heterozygotes with the NBN Founder Mutation","volume":"99","author":"Seemanova","year":"2007","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/sj.ejhg.5200554","article-title":"Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations","volume":"8","author":"Varon","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/86920","article-title":"An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele","volume":"27","author":"Maser","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrm3047","article-title":"The MRE11 complex: Starting from the ends","volume":"12","author":"Stracker","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1128\/MCB.17.9.5016","article-title":"Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation","volume":"17","author":"Jongmans","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1128\/MCB.21.15.5214-5222.2001","article-title":"Chk2 activation dependence on Nbs1 after DNA damage","volume":"21","author":"Buscemi","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1006\/clin.1996.4275","article-title":"Cell Cycle Checkpoints and DNA Repair in Nijmegen Breakage Syndrome","volume":"82","author":"Sullivan","year":"1997","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nm1228","article-title":"An essential function for NBS1 in the prevention of ataxia and cerebellar defects","volume":"11","author":"Frappart","year":"2005","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.dnarep.2011.10.021","article-title":"Differential function of NBS1 and ATR in neurogenesis","volume":"11","author":"Zhou","year":"2012","journal-title":"DNA Repair"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rodrigues, P.M.G., Grigaravicius, P., Remus, M., Cavalheiro, G.R., Gomes, A.L., Martins, M.R., Frappart, L., Reuss, D., McKinnon, P.J., and von Deimling, A. (2013). Nbn and Atm Cooperate in a Tissue and Developmental Stage-Specific Manner to Prevent Double Strand Breaks and Apoptosis in Developing Brain and Eye. PLoS ONE, 8.","DOI":"10.1371\/annotation\/b38f50e0-04b6-42c5-8b19-50be747a38f3"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s13238-017-0479-2","article-title":"Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease","volume":"8","author":"Li","year":"2017","journal-title":"Protein Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10924","DOI":"10.1093\/nar\/gkaa716","article-title":"NBS1 interacts with Notch signaling in neuronal homeostasis","volume":"48","author":"Zhou","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.scr.2015.10.013","article-title":"Generation of iPSC lines from a Nijmegen Breakage Syndrome patient","volume":"15","author":"Mlody","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7516","DOI":"10.1038\/s41598-017-07905-2","article-title":"Nijmegen Breakage Syndrome fibroblasts and iPSCs: Cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants","volume":"7","author":"Mlody","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/j.celrep.2016.07.071","article-title":"Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients","volume":"16","author":"Halevy","year":"2016","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.scr.2017.10.004","article-title":"Derivation and characterization of integration-free iPSC line ISRM-UM51 derived from SIX2-positive renal cells isolated from urine of an African male expressing the CYP2D6 *4\/*17 variant which confers intermediate drug metabolizing activity","volume":"25","author":"Bohndorf","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101372","DOI":"10.1016\/j.scr.2018.101372","article-title":"Fibroblast-derived integration-free iPSC line ISRM-NBS1 from an 18-year-old Nijmegen Breakage Syndrome patient carrying the homozygous NBN c.657_661del5 mutation","volume":"34","author":"Martins","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s12015-010-9209-3","article-title":"A Cyclic AMP Analog, 8-Br-cAMP, Enhances the Induction of Pluripotency in Human Fibroblast Cells","volume":"7","author":"Wang","year":"2011","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1038\/s41596-018-0032-7","article-title":"Generation and assembly of human brain region\u2013specific three-dimensional cultures","volume":"13","author":"Sloan","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: Open software development for computational biology and bioinformatics","volume":"5","author":"Gentleman","year":"2004","journal-title":"Genome Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1093\/bioinformatics\/btq431","article-title":"A framework for oligonucleotide microarray preprocessing","volume":"26","author":"Carvalho","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_28","first-page":"1","article-title":"gplots: Various R Programming Tools for Plotting Data","volume":"2","author":"Warnes","year":"2015","journal-title":"R Package Vers"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chen, H., and Boutros, P.C. (2011). VennDiagram: A package for the generation of highly-customizable Venn and Euler diagrams in R. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-35"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1089\/scd.2015.0383","article-title":"Modeling Nonalcoholic Fatty Liver Disease with Human Pluripotent Stem Cell-Derived Immature Hepatocyte-Like Cells Reveals Activation of PLIN2 and Confirms Regulatory Functions of Peroxisome Proliferator-Activated Receptor Alpha","volume":"25","author":"Graffmann","year":"2016","journal-title":"Stem Cells Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/nrn2722","article-title":"The allen brain atlas: 5 years and beyond","volume":"10","author":"Jones","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"H\u00e4nzelmann, S., Castelo, R., and Guinney, J. (2013). GSVA: Gene set variation analysis for microarray and RNA-Seq data. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-7"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Smyth, G.K. (2004). Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments. Stat. Appl. Genet. Mol. Biol., 3.","DOI":"10.2202\/1544-6115.1027"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/1467-9868.00346","article-title":"A direct approach to false discovery rates","volume":"64","author":"Storey","year":"2002","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration","volume":"14","author":"Robinson","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1038\/s41598-020-60796-8","article-title":"Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1","volume":"10","author":"Erichsen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"W170","DOI":"10.1093\/nar\/gkn294","article-title":"QUMA: Quantification tool for methylation analysis","volume":"36","author":"Kumaki","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature13185","article-title":"Transcriptional landscape of the prenatal human brain","volume":"508","author":"Miller","year":"2014","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fneur.2020.00148","article-title":"Therapeutic Plasticity of Neural Stem Cells","volume":"11","author":"Ottoboni","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"i11","DOI":"10.1093\/jrr\/rrw031","article-title":"NBS1 and multiple regulations of DNA damage response","volume":"57","author":"Komatsu","year":"2016","journal-title":"J. Radiat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/0092-8674(93)90500-P","article-title":"WAF1, a potential mediator of p53 tumor suppression","volume":"75","author":"Tokino","year":"1993","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/jcp.25498","article-title":"Neuronatin Protein in Health and Disease","volume":"232","author":"Pitale","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1089\/scd.2015.0061","article-title":"Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage","volume":"24","author":"Sobol","year":"2015","journal-title":"Stem Cells Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pediatrneurol.2003.07.003","article-title":"Nijmegen breakage syndrome in 13% of age-matched Czech children with primary microcephaly","volume":"30","author":"Seeman","year":"2004","journal-title":"Pediatric Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"803","DOI":"10.15252\/embj.201593679","article-title":"CPAP promotes timely cilium disassembly to maintain neural progenitor pool","volume":"35","author":"Gabriel","year":"2016","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/s41467-019-10497-2","article-title":"Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1126\/science.abb5390","article-title":"A human tissue screen identifies a regulator of ER secretion as a brain-size determinant","volume":"370","author":"Esk","year":"2020","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.molcel.2016.04.006","article-title":"Epigenome Maintenance in Response to DNA Damage","volume":"62","author":"Dabin","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.molmed.2017.02.001","article-title":"p21: A Two-Faced Genome Guardian","volume":"23","author":"Georgakilas","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1128\/MCB.26.5.1691-1699.2006","article-title":"Active Role for Nibrin in the Kinetics of Atm Activation","volume":"26","author":"Cerosaletti","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.celrep.2013.12.018","article-title":"The essential function of the MRN complex in the resolution of endogenous replication intermediates","volume":"6","author":"Bruhn","year":"2014","journal-title":"Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e12972","DOI":"10.1111\/cpr.12972","article-title":"Nbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis","volume":"54","author":"Chen","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1182\/blood-2005-12-5148","article-title":"Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia","volume":"108","author":"Kojima","year":"2006","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/humu.23955","article-title":"DNA repair functional analyses of NBN hypomorphic variants associated with NBN-related infertility","volume":"41","author":"Bellanger","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1093\/emboj\/cdg541","article-title":"Requirement of the MRN complex for ATM activation by DNA damage","volume":"22","author":"Uziel","year":"2003","journal-title":"EMBO J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/cr.2015.85","article-title":"DNA damage and repair regulate neuronal gene expression","volume":"25","author":"Su","year":"2015","journal-title":"Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Niklison-Chirou, M.V., Agostini, M., Amelio, I., and Melino, G. (2020). Regulation of Adult Neurogenesis in Mammalian Brain. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144869"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/stem.530","article-title":"Neuronatin promotes neural lineage in ESCs via Ca2+ signaling","volume":"28","author":"Lin","year":"2010","journal-title":"Stem Cells (Dayt. Ohio)"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2016.04.023","article-title":"Neuronatin is a stress-responsive protein of rod photoreceptors","volume":"328","author":"Shinde","year":"2016","journal-title":"Neuroscience"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ygeno.2013.12.001","article-title":"Neuronatin gene: Imprinted and misfolded. Studies in Lafora disease, diabetes and cancer may implicate NNAT-aggregates as a common downstream participant in neuronal loss","volume":"103","author":"Joseph","year":"2014","journal-title":"Genomics"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/5\/802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:27:31Z","timestamp":1760135251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/5\/802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":64,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cells11050802"],"URL":"https:\/\/doi.org\/10.3390\/cells11050802","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.29.318527","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]}}}