{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:21:12Z","timestamp":1791948072807,"version":"4.3.4"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson&apos;s UK","doi-asserted-by":"publisher","award":["J-1403"],"award-info":[{"award-number":["J-1403"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson&apos;s UK","doi-asserted-by":"publisher","award":["J-1403"],"award-info":[{"award-number":["J-1403"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson&apos;s UK","doi-asserted-by":"publisher","award":["J-1403"],"award-info":[{"award-number":["J-1403"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson&apos;s UK","doi-asserted-by":"publisher","award":["J-1403"],"award-info":[{"award-number":["J-1403"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Parkinson&apos;s UK"},{"name":"Parkinson&apos;s UK"},{"DOI":"10.13039\/501100004211","name":"Oxford University | Oxford Martin School, University of Oxford","doi-asserted-by":"publisher","award":["LC0910-004"],"award-info":[{"award-number":["LC0910-004"]}],"id":[{"id":"10.13039\/501100004211","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Parkinson&apos;s UK"},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L023784\/2"],"award-info":[{"award-number":["MR\/L023784\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M024962\/1"],"award-info":[{"award-number":["MR\/M024962\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) is an age-related neurodegenerative condition and the most common type of dementia, characterised by pathological accumulation of extracellular plaques and intracellular neurofibrillary tangles that mainly consist of amyloid-\u03b2 (A\u03b2) and hyperphosphorylated tau aggregates, respectively. Previous studies in mouse models with a targeted knock-out of the microtubule-associated protein tau\n                    <jats:italic>(Mapt)<\/jats:italic>\n                    gene demonstrated that A\u03b2-driven toxicity is tau-dependent. However, human cellular models with chronic tau lowering remain unexplored. In this study, we generated stable tau-depleted human induced pluripotent stem cell (iPSC) isogenic panels from two healthy individuals using CRISPR-Cas9 technology. We then differentiated these iPSCs into cortical neurons in vitro in co-culture with primary rat cortical astrocytes before conducting electrophysiological and imaging experiments for a wide range of disease-relevant phenotypes. Both AD brain derived and recombinant A\u03b2 were used in this study to elicit toxic responses from the iPSC-derived cortical neurons. We showed that tau depletion in human iPSC-derived cortical neurons caused considerable reductions in neuronal activity without affecting synaptic density. We also observed neurite outgrowth impairments in two of the tau-depleted lines used. Finally, tau depletion protected neurons from adverse effects\u00a0by mitigating the impact of exogenous A\u03b2-induced hyperactivity, deficits in retrograde axonal transport of mitochondria, and neurodegeneration. Our study established stable human iPSC isogenic panels with chronic tau depletion from two healthy individuals. Cortical neurons derived from these iPSC lines showed that tau is essential in A\u03b2-driven hyperactivity, axonal transport deficits, and neurodegeneration, consistent with studies conducted in\n                    <jats:italic>Mapt\u2212\/\u2212<\/jats:italic>\n                    mouse models. These findings highlight the protective effects of chronic tau lowering strategies in AD pathogenesis and reinforce the potential in clinical settings. The tau-depleted human iPSC models can now be applied at scale to investigate the involvement of tau in disease-relevant pathways and cell types.\n                  <\/jats:p>","DOI":"10.1038\/s41380-024-02463-2","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T07:02:58Z","timestamp":1707980578000},"page":"2009-2020","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Tau depletion in human neurons mitigates A\u03b2-driven toxicity"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6819-0176","authenticated-orcid":false,"given":"Bryan","family":"Ng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Vowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-6663","authenticated-orcid":false,"given":"F\u00e9odora","family":"Bertherat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-8001","authenticated-orcid":false,"given":"Ajantha","family":"Abey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kilfeather","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayne","family":"Beccano-Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Irina","family":"Stefana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4924-7795","authenticated-orcid":false,"given":"Darragh P.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Bengoa-Vergniory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillippa J.","family":"Carling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Todd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara M.","family":"Caffrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Connor-Robson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-6675","authenticated-orcid":false,"given":"Sally A.","family":"Cowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Wade-Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"2463_CR1","doi-asserted-by":"publisher","first-page":"a006189","DOI":"10.1101\/cshperspect.a006189","volume":"1","author":"A Serrano-Pozo","year":"2011","unstructured":"Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological Alterations in Alzheimer Disease. Cold Spring Harb Perspect Med. 2011;1:a006189.","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2463_CR2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 2018;14:535.","journal-title":"Alzheimers Dement"},{"key":"2463_CR3","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1001\/jamaneurol.2019.1424","volume":"76","author":"BJ Hanseeuw","year":"2019","unstructured":"Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA, et al. Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study. JAMA Neurol. 2019;76:915\u201324.","journal-title":"JAMA Neurol"},{"key":"2463_CR4","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1073\/pnas.1017033108","volume":"108","author":"M Jin","year":"2011","unstructured":"Jin M, Shepardson N, Yang T, Chen G, Walsh D, Selkoe DJ. Soluble amyloid \u03b2-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci USA. 2011;108:5819\u201324.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2463_CR5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/0165-6147(91)90609-V","volume":"12","author":"J Hardy","year":"1991","unstructured":"Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer\u2019s disease. Trends Pharm Sci. 1991;12:383\u20138.","journal-title":"Trends Pharm Sci"},{"key":"2463_CR6","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1126\/science.1566067","volume":"256","author":"JA Hardy","year":"1992","unstructured":"Hardy JA, Higgins GA. Alzheimer\u2019s disease: The amyloid cascade hypothesis. Science 1992;256:184\u20135.","journal-title":"Science"},{"key":"2463_CR7","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1523\/JNEUROSCI.2610-10.2011","volume":"31","author":"OA Shipton","year":"2011","unstructured":"Shipton OA, Leitz JR, Dworzak J, Acton CEJ, Tunbridge EM, Denk F, et al. Tau Protein Is Required for Amyloid \u03b2-Induced Impairment of Hippocampal Long-Term Potentiation. J Neurosci 2011;31:1688\u201392.","journal-title":"J Neurosci"},{"key":"2463_CR8","first-page":"8","volume":"041787","author":"KA Vossel","year":"2010","unstructured":"Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, et al. Tau Reduction Prevents Abeta-Induced Defects in Axonal Transport. Science 2010;041787:8\u201310. (October)","journal-title":"Science"},{"key":"2463_CR9","doi-asserted-by":"publisher","first-page":"6364","DOI":"10.1073\/pnas.092136199","volume":"99","author":"M Rapoport","year":"2002","unstructured":"Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A. Tau is essential to beta-amyloid-induced neurotoxicity. Proc Natl Acad Sci USA. 2002;99:6364\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2463_CR10","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1126\/science.1141736","volume":"316","author":"ED Roberson","year":"2007","unstructured":"Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. Reducing Endogenous Tau Ameliorates Amyloid \u00df-Induced Deficits in an Alzheimer\u2019s Disease Mouse Model. Science 2007;316:750\u20134.","journal-title":"Science"},{"key":"2463_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1750-1326-9-29","volume":"9","author":"P Lei","year":"2014","unstructured":"Lei P, Ayton S, Moon S, Zhang Q, Volitakis I, Finkelstein DI, et al. Motor and cognitive deficits in aged tau knockout mice in two background strains. Mol Neurodegener. 2014;9:1\u201312.","journal-title":"Mol Neurodegener"},{"key":"2463_CR12","first-page":"873270","volume":"2012","author":"YD Ke","year":"2012","unstructured":"Ke YD, Suchowerska AK, Van Der Hoven J, De Silva DM, Wu CW, Van Eersel J, et al. Lessons from Tau-deficient mice. Int J Alzheimers Dis. 2012;2012:873270.","journal-title":"Int J Alzheimers Dis"},{"key":"2463_CR13","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.neuron.2010.04.031","volume":"66","author":"KH Ashe","year":"2010","unstructured":"Ashe KH, Zahs KR. Probing the biology of Alzheimer\u2019s disease in mice. Neuron. 2010;66:631.","journal-title":"Neuron"},{"key":"2463_CR14","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/0896-6273(89)90077-9","volume":"2","author":"KS Kosik","year":"1989","unstructured":"Kosik KS, Orecchio LD, Bakalis S, Neve RL. Developmentally regulated expression of specific tau sequences. Neuron. 1989;2:1389\u201397.","journal-title":"Neuron"},{"key":"2463_CR15","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861\u201372.","journal-title":"Cell"},{"key":"2463_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0141-1","volume":"9","author":"D Melguizo-Sanchis","year":"2018","unstructured":"Melguizo-Sanchis D, Xu Y, Taheem D, Yu M, Tilgner K, Barta T, et al. iPSC modeling of severe aplastic anemia reveals impaired differentiation and telomere shortening in blood progenitors. Cell Death Dis. 2018;9:128.","journal-title":"Cell Death Dis"},{"key":"2463_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09362-3","volume":"7","author":"W Haenseler","year":"2017","unstructured":"Haenseler W, Zambon F, Lee H, Vowles J, Rinaldi F, Duggal G, et al. Excess \u03b1-synuclein compromises phagocytosis in iPSC-derived macrophages. Sci Rep. 2017;7:9003.","journal-title":"Sci Rep"},{"key":"2463_CR18","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676\u201382. 2012 97","journal-title":"Nat Methods"},{"key":"2463_CR19","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","volume":"115","author":"JY Tinevez","year":"2017","unstructured":"Tinevez JY, Perry N, Schindelin J, Hoopes GM, Reynolds GD, Laplantine E, et al. TrackMate: An open and extensible platform for single-particle tracking. Methods. 2017;115:80\u201390.","journal-title":"Methods"},{"key":"2463_CR20","doi-asserted-by":"crossref","unstructured":"Ellis MJ, Lekka C, Tulmin H, O\u2019Brien DP, Dhayal S, Zeissler M-L, et al. Validation of Tau Antibodies for Use in Western Blotting and Immunohistochemistry. BioRxiv. 2023. https:\/\/www.biorxiv.org\/content\/10.1101\/2023.04.13.536711v1.","DOI":"10.1101\/2023.04.13.536711"},{"key":"2463_CR21","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1083\/jcb.101.4.1371","volume":"101","author":"LI Binder","year":"1985","unstructured":"Binder LI, Frankfurter A, Rebhun LI. The distribution of tau in the mammalian central nervous system. J Cell Biol. 1985;101:1371\u20138.","journal-title":"J Cell Biol"},{"key":"2463_CR22","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1242\/jcs.114.6.1179","volume":"114","author":"HN Dawson","year":"2001","unstructured":"Dawson HN, Ferreira A, Eyster MV, Ghoshal N, Binder LI, Vitek MP. Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J Cell Sci. 2001;114:1179\u201387.","journal-title":"J Cell Sci"},{"key":"2463_CR23","doi-asserted-by":"publisher","first-page":"109855","DOI":"10.1016\/j.celrep.2021.109855","volume":"37","author":"CW Chang","year":"2021","unstructured":"Chang CW, Evans MD, Yu X, Yu GQ, Mucke L. Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation\/inhibition ratios, and counteracts network hypersynchrony. Cell Rep. 2021;37:109855.","journal-title":"Cell Rep"},{"key":"2463_CR24","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1002\/ana.22105","volume":"68","author":"YT Quiroz","year":"2010","unstructured":"Quiroz YT, Budson AE, Celone K, Ruiz A, Newmark R, Castrill\u00f5n G, et al. Hippocampal hyperactivation in presymptomatic familial Alzheimer\u2019s disease. Ann Neurol. 2010;68:865\u201375.","journal-title":"Ann Neurol"},{"key":"2463_CR25","doi-asserted-by":"publisher","first-page":"3592","DOI":"10.1016\/j.celrep.2019.11.044","volume":"29","author":"EK Pickett","year":"2019","unstructured":"Pickett EK, Herrmann AG, McQueen J, Abt K, Dando O, Tulloch J, et al. Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer\u2019s Disease. Cell Rep. 2019;29:3592\u2013.e5.","journal-title":"Cell Rep"},{"key":"2463_CR26","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1126\/science.1162844","volume":"321","author":"MA Busche","year":"2008","unstructured":"Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, et al. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer\u2019s disease. Science. 2008;321:1686\u20139.","journal-title":"Science."},{"key":"2463_CR27","doi-asserted-by":"publisher","first-page":"fcac267","DOI":"10.1093\/braincomms\/fcac267","volume":"4","author":"B Ng","year":"2022","unstructured":"Ng B, Rowland HA, Wei T, Arunasalam K, Hayes EM, Koychev I, et al. Neurons derived from individual early Alzheimer\u2019s disease patients reflect their clinical vulnerability. Brain Commun. 2022;4:fcac267.","journal-title":"Brain Commun"},{"key":"2463_CR28","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1038\/369488a0","volume":"369","author":"A Harada","year":"1994","unstructured":"Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, et al. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. 1994;369:488\u201391.","journal-title":"Nature"},{"key":"2463_CR29","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1083\/jcb.201407065","volume":"209","author":"KA Vossel","year":"2015","unstructured":"Vossel KA, Xu JC, Fomenko V, Miyamoto T, Suberbielle E, Knox JA, et al. Tau reduction prevents A\u03b2-induced axonal transport deficits by blocking activation of GSK3\u03b2. J Cell Biol. 2015;209:419\u201333.","journal-title":"J Cell Biol"},{"key":"2463_CR30","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1016\/j.bbamem.2018.02.022","volume":"1860","author":"MFM Sciacca","year":"2018","unstructured":"Sciacca MFM, Tempra C, Scollo F, Milardi D, La Rosa C. Amyloid growth and membrane damage: Current themes and emerging perspectives from theory and experiments on A\u03b2 and hIAPP. Biochim Biophys Acta Biomembr. 2018;1860:1625\u201338.","journal-title":"Biochim Biophys Acta Biomembr"},{"key":"2463_CR31","doi-asserted-by":"publisher","first-page":"e180","DOI":"10.1038\/mtna.2014.30","volume":"3","author":"R Sud","year":"2014","unstructured":"Sud R, Geller ET, Schellenberg GD. Antisense-mediated Exon Skipping Decreases Tau Protein Expression: A Potential Therapy For Tauopathies. Mol Ther Nucleic Acids. 2014;3:e180.","journal-title":"Mol Ther Nucleic Acids"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02463-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02463-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02463-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T07:00:05Z","timestamp":1726729205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02463-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["2463"],"URL":"https:\/\/doi.org\/10.1038\/s41380-024-02463-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.12.23.521772","asserted-by":"object"}]},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]},"assertion":[{"value":"14 February 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The ethics information for the SBAd-03-01 parental iPSC line can be found from the Lonza product page (CC-2511) where the source dermal fibroblast was obtained, whereas that for the SFC856-03-04 parental iPSC line was approved by the National Health Service, Health Research Authority, National Research Ethics Service Committee South Central, Berkshire, United Kingdom, Research Ethics Committee 10\/H0505\/71.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}