{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:37:04Z","timestamp":1792795024372,"version":"4.5.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","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\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["82271280"],"award-info":[{"award-number":["82271280"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["82301433"],"award-info":[{"award-number":["82301433"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflamm Regener"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Different neural subtypes are selectively lost in diverse neurodegenerative diseases. Huntington\u2019s disease (HD) is an inherited neurodegenerative disease characterized by motor abnormalities that primarily affect the striatum. The Huntingtin (HTT) mutation involves an expanded CAG repeat, leading to insoluble polyQ, which renders GABA<jats:sup>+<\/jats:sup> medium spiny neurons (MSN) more venerable to cell death. Human pluripotent stem cells (hPSCs) technology allows for the construction of disease-specific models, providing valuable cellular models for studying pathogenesis, drug screening, and high-throughput analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this study, we established a method that allows for rapid and efficient generation of MSNs (&gt;\u200990%) within 21\u00a0days from hPSC-derived neural progenitor cells, by introducing a specific combination of transcription factors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We efficiently induced several neural subtypes, in parallel, based on the same cell source, and revealed that, compared to other neural subtypes, MSNs exhibited higher polyQ aggregation propensity and overexpression toxicity, more severe dysfunction in BDNF\/TrkB signaling, greater susceptibility to BDNF withdrawal, and more severe disturbances in nucleocytoplasmic transport (NCT). We further found that the nuclear lamina protein LMNB1 was greatly reduced in HD neurons and mislocalized to the cytoplasm and axons. Knockdown of HTT or treatment with KPT335, an orally selective inhibitor of nuclear export (SINE), effectively attenuated the pathological phenotypes and alleviated neuronal death caused by BDNF withdrawal.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study thus establishes an effective method for obtaining MSNs and underscores the necessity of using high-purity MSNs to study HD pathogenesis, especially the MSN-selective vulnerability.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s41232-024-00320-x","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T20:02:22Z","timestamp":1708027342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Rapid and high-purity differentiation of human medium spiny neurons reveals LMNB1 hypofunction and subtype necessity in modeling Huntington\u2019s disease"],"prefix":"10.1186","volume":"44","author":[{"given":"Junjiao","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-9614","authenticated-orcid":false,"given":"Yu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"320_CR1","doi-asserted-by":"publisher","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","volume":"1","author":"GP Bates","year":"2015","unstructured":"Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, et al. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.","journal-title":"Nat Rev Dis Primers"},{"key":"320_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3233\/JHD-2012-120018","volume":"1","author":"HJ Waldvogel","year":"2012","unstructured":"Waldvogel HJ, Kim EH, Thu DC, Tippett LJ, Faull RL. New perspectives on the neuropathology in Huntington\u2019s disease in the human brain and its relation to symptom variation. J Huntingtons Dis. 2012;1:143\u201353.","journal-title":"J Huntingtons Dis"},{"key":"320_CR3","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.nbd.2010.07.014","volume":"40","author":"PC Nopoulos","year":"2010","unstructured":"Nopoulos PC, Aylward EH, Ross CA, Johnson HJ, Magnotta VA, Juhl AR, et al. Cerebral cortex structure in prodromal Huntington disease. Neurobiol Dis. 2010;40:544\u201354.","journal-title":"Neurobiol Dis"},{"key":"320_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1755-5949.2008.00068.x","volume":"15","author":"F Squitieri","year":"2009","unstructured":"Squitieri F, Cannella M, Simonelli M, Sassone J, Martino T, Venditti E, et al. Distinct brain volume changes correlating with clinical stage, disease progression rate, mutation size, and age at onset prediction as early biomarkers of brain atrophy in Huntington\u2019s disease. CNS Neurosci Ther. 2009;15:1\u201311.","journal-title":"CNS Neurosci Ther"},{"key":"320_CR5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1159\/000339528","volume":"12","author":"I Dogan","year":"2013","unstructured":"Dogan I, Eickhoff SB, Schulz JB, Shah NJ, Laird AR, Fox PT, et al. Consistent neurodegeneration and its association with clinical progression in Huntington\u2019s disease: a coordinate-based meta-analysis. Neurodegener Dis. 2013;12:23\u201335.","journal-title":"Neurodegener Dis"},{"key":"320_CR6","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/nrn1806","volume":"6","author":"E Cattaneo","year":"2005","unstructured":"Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: an alternative approach to Huntington\u2019s disease. Nat Rev Neurosci. 2005;6:919\u201330.","journal-title":"Nat Rev Neurosci"},{"key":"320_CR7","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1002\/sctm.20-0431","volume":"10","author":"H Dahlenburg","year":"2021","unstructured":"Dahlenburg H, Cameron D, Yang S, Bachman A, Pollock K, Cary W, et al. A novel Huntington\u2019s disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies. Stem Cells Transl Med. 2021;10:1033\u201343.","journal-title":"Stem Cells Transl Med"},{"key":"320_CR8","doi-asserted-by":"publisher","first-page":"e2022940118","DOI":"10.1073\/pnas.2022940118","volume":"118","author":"S Peng","year":"2021","unstructured":"Peng S, Guo P, Lin X, An Y, Sze KH, Lau MHY, et al. CAG RNAs induce DNA damage and apoptosis by silencing NUDT16 expression in polyglutamine degeneration. Proc Natl Acad Sci U S A. 2021;118:e2022940118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"320_CR9","doi-asserted-by":"publisher","first-page":"6182","DOI":"10.1523\/JNEUROSCI.0857-08.2008","volume":"28","author":"M Gray","year":"2008","unstructured":"Gray M, Shirasaki DI, Cepeda C, Andre VM, Wilburn B, Lu XH, et al. Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci. 2008;28:6182\u201395.","journal-title":"J Neurosci"},{"key":"320_CR10","doi-asserted-by":"publisher","first-page":"e13082","DOI":"10.1111\/cpr.13082","volume":"54","author":"HJ Park","year":"2021","unstructured":"Park HJ, Jeon J, Choi J, Kim JY, Kim HS, Huh JY, et al. Human iPSC-derived neural precursor cells differentiate into multiple cell types to delay disease progression following transplantation into YAC128 Huntington\u2019s disease mouse model. Cell Prolif. 2021;54:e13082.","journal-title":"Cell Prolif"},{"key":"320_CR11","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.neuron.2012.05.009","volume":"74","author":"HB Kordasiewicz","year":"2012","unstructured":"Kordasiewicz HB, Stanek LM, Wancewicz EV, Mazur C, McAlonis MM, Pytel KA, et al. Sustained therapeutic reversal of Huntington\u2019s disease by transient repression of huntingtin synthesis. Neuron. 2012;74:1031\u201344.","journal-title":"Neuron"},{"key":"320_CR12","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.3390\/ijms19082398","volume":"19","author":"A Rosas-Arellano","year":"2018","unstructured":"Rosas-Arellano A, Estrada-Mondragon A, Pina R, Mantellero CA, Castro MA. The tiny drosophila melanogaster for the biggest answers in Huntington\u2019s disease. Int J Mol Sci. 2018;19:2398.","journal-title":"Int J Mol Sci"},{"issue":"989\u20131002","key":"320_CR13","volume":"173","author":"S Yan","year":"2018","unstructured":"Yan S, Tu Z, Liu Z, Fan N, Yang H, Yang S, et al. A Huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington\u2019s disease. Cell. 2018;173(989\u20131002): e13.","journal-title":"Cell"},{"key":"320_CR14","doi-asserted-by":"publisher","first-page":"eaaq1818","DOI":"10.1126\/scitranslmed.aaq1818","volume":"11","author":"EMC Fisher","year":"2019","unstructured":"Fisher EMC, Bannerman DM. Mouse models of neurodegeneration: Know your question, know your mouse. Sci Transl Med. 2019;11:eaaq1818.","journal-title":"Sci Transl Med."},{"key":"320_CR15","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.15252\/embj.201591267","volume":"34","author":"JK Ichida","year":"2015","unstructured":"Ichida JK, Kiskinis E. Probing disorders of the nervous system using reprogramming approaches. EMBO J. 2015;34:1456\u201377.","journal-title":"EMBO J"},{"key":"320_CR16","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s41232-020-00149-0","volume":"40","author":"N Nagoshi","year":"2020","unstructured":"Nagoshi N, Okano H, Nakamura M. Regenerative therapy for spinal cord injury using iPSC technology. Inflamm Regen. 2020;40:40.","journal-title":"Inflamm Regen"},{"key":"320_CR17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s41232-023-00269-3","volume":"43","author":"A Morizane","year":"2023","unstructured":"Morizane A. Cell therapy for Parkinson\u2019s disease with induced pluripotent stem cells. Inflamm Regen. 2023;43:16.","journal-title":"Inflamm Regen"},{"key":"320_CR18","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1242\/dev.117093","volume":"142","author":"C Arber","year":"2015","unstructured":"Arber C, Precious SV, Cambray S, Risner-Janiczek JR, Kelly C, Noakes Z, et al. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells. Development. 2015;142:1375\u201386.","journal-title":"Development"},{"key":"320_CR19","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1007\/s13311-011-0079-4","volume":"8","author":"C Nicoleau","year":"2011","unstructured":"Nicoleau C, Viegas P, Peschanski M, Perrier AL. Human pluripotent stem cell therapy for Huntington\u2019s disease: technical, immunological, and safety challenges human pluripotent stem cell therapy for Huntington\u2019s disease: technical, immunological, and safety challenges. Neurotherapeutics. 2011;8:562\u201376.","journal-title":"Neurotherapeutics"},{"key":"320_CR20","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.expneurol.2016.01.021","volume":"278","author":"MM Golas","year":"2016","unstructured":"Golas MM, Sander B. Use of human stem cells in Huntington disease modeling and translational research. Exp Neurol. 2016;278:76\u201390.","journal-title":"Exp Neurol"},{"key":"320_CR21","doi-asserted-by":"publisher","first-page":"16707","DOI":"10.1073\/pnas.0808488105","volume":"105","author":"L Aubry","year":"2008","unstructured":"Aubry L, Bugi A, Lefort N, Rousseau F, Peschanski M, Perrier AL. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci U S A. 2008;105:16707\u201312.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"320_CR22","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.stem.2012.01.021","volume":"10","author":"L Ma","year":"2012","unstructured":"Ma L, Hu B, Liu Y, Vermilyea SC, Liu H, Gao L, et al. Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice. Cell Stem Cell. 2012;10:455\u201364.","journal-title":"Cell Stem Cell"},{"key":"320_CR23","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.stem.2012.04.027","volume":"11","author":"Consortium HDi","year":"2012","unstructured":"Consortium HDi. Induced pluripotent stem cells from patients with Huntington\u2019s disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell. 2012;11:264\u201378.","journal-title":"Cell Stem Cell"},{"key":"320_CR24","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.stemcr.2018.08.005","volume":"11","author":"M Wu","year":"2018","unstructured":"Wu M, Zhang D, Bi C, Mi T, Zhu W, Xia L, et al. A chemical recipe for generation of clinical-grade striatal neurons from hESCs. Stem Cell Reports. 2018;11:635\u201350.","journal-title":"Stem Cell Reports"},{"key":"320_CR25","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41580-021-00335-z","volume":"22","author":"H Wang","year":"2021","unstructured":"Wang H, Yang Y, Liu J, Qian L. Direct cell reprogramming: approaches, mechanisms and progress. Nat Rev Mol Cell Biol. 2021;22:410\u201324.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"320_CR26","doi-asserted-by":"publisher","first-page":"102284","DOI":"10.1016\/j.pneurobio.2022.102284","volume":"214","author":"SG Yang","year":"2022","unstructured":"Yang SG, Wang XW, Qian C, Zhou FQ. Reprogramming neurons for regeneration: the fountain of youth. Prog Neurobiol. 2022;214:102284.","journal-title":"Prog Neurobiol"},{"key":"320_CR27","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1089\/cell.2021.0045","volume":"23","author":"I Canals","year":"2021","unstructured":"Canals I, Quist E, Ahlenius H. Transcription factor-based strategies to generate neural cell types from human pluripotent stem cells. Cell Reprogram. 2021;23:206\u201320.","journal-title":"Cell Reprogram"},{"key":"320_CR28","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/s41587-020-0742-6","volume":"39","author":"AHM Ng","year":"2021","unstructured":"Ng AHM, Khoshakhlagh P, Rojo Arias JE, Pasquini G, Wang K, Swiersy A, et al. A comprehensive library of human transcription factors for cell fate engineering. Nat Biotechnol. 2021;39:510\u20139.","journal-title":"Nat Biotechnol"},{"issue":"209\u2013229","key":"320_CR29","first-page":"e26","volume":"186","author":"J Joung","year":"2023","unstructured":"Joung J, Ma S, Tay T, Geiger-Schuller KR, Kirchgatterer PC, Verdine VK, et al. A transcription factor atlas of directed differentiation. Cell. 2023;186(209\u2013229):e26.","journal-title":"Cell"},{"key":"320_CR30","doi-asserted-by":"publisher","first-page":"108460","DOI":"10.1016\/j.celrep.2020.108460","volume":"33","author":"JB Black","year":"2020","unstructured":"Black JB, McCutcheon SR, Dube S, Barrera A, Klann TS, Rice GA, et al. Master regulators and cofactors of human neuronal cell fate specification identified by CRISPR gene activation screens. Cell Rep. 2020;33:108460.","journal-title":"Cell Rep"},{"key":"320_CR31","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","volume":"78","author":"Y Zhang","year":"2013","unstructured":"Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 2013;78:785\u201398.","journal-title":"Neuron"},{"key":"320_CR32","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1038\/ncomms3183","volume":"4","author":"ML Liu","year":"2013","unstructured":"Liu ML, Zang T, Zou Y, Chang JC, Gibson JR, Huber KM, et al. Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into cholinergic neurons. Nat Commun. 2013;4:2183.","journal-title":"Nat Commun"},{"key":"320_CR33","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1016\/j.stemcr.2021.05.017","volume":"16","author":"YH Ng","year":"2021","unstructured":"Ng YH, Chanda S, Janas JA, Yang N, Kokubu Y, Sudhof TC, et al. Efficient generation of dopaminergic induced neuronal cells with midbrain characteristics. Stem Cell Reports. 2021;16:1763\u201376.","journal-title":"Stem Cell Reports"},{"key":"320_CR34","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.stemcr.2020.08.013","volume":"15","author":"S Nolbrant","year":"2020","unstructured":"Nolbrant S, Giacomoni J, Hoban DB, Bruzelius A, Birtele M, Chandler-Militello D, et al. Direct reprogramming of human fetal- and stem cell-derived glial progenitor cells into midbrain dopaminergic neurons. Stem Cell Reports. 2020;15:869\u201382.","journal-title":"Stem Cell Reports"},{"key":"320_CR35","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nmeth.4291","volume":"14","author":"N Yang","year":"2017","unstructured":"Yang N, Chanda S, Marro S, Ng YH, Janas JA, Haag D, et al. Generation of pure GABAergic neurons by transcription factor programming. Nat Methods. 2017;14:621\u20138.","journal-title":"Nat Methods"},{"key":"320_CR36","doi-asserted-by":"publisher","first-page":"108548","DOI":"10.1016\/j.jneumeth.2019.108548","volume":"334","author":"N Barretto","year":"2020","unstructured":"Barretto N, Zhang H, Powell SK, Fernando MB, Zhang S, Flaherty EK, et al. ASCL1- and DLX2-induced GABAergic neurons from hiPSC-derived NPCs. J Neurosci Methods. 2020;334:108548.","journal-title":"J Neurosci Methods"},{"key":"320_CR37","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/978-1-0716-2811-9_16","volume":"2593","author":"J Wu","year":"2023","unstructured":"Wu J, Tang Y. Transcription factor-mediated differentiation of motor neurons from human pluripotent stem cells. Methods Mol Biol. 2023;2593:245\u201358.","journal-title":"Methods Mol Biol"},{"key":"320_CR38","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.3390\/cells10113087","volume":"10","author":"J Ren","year":"2021","unstructured":"Ren J, Li C, Zhang M, Wang H, Xie Y, Tang Y. A Step-by-step refined strategy for highly efficient generation of neural progenitors and motor neurons from human pluripotent stem cells. Cells. 2021;10:3087.","journal-title":"Cells"},{"key":"320_CR39","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3389\/fnmol.2017.00359","volume":"10","author":"Y Tang","year":"2017","unstructured":"Tang Y, Liu ML, Zang T, Zhang CL. Direct reprogramming rather than iPSC-based reprogramming maintains aging hallmarks in human motor neurons. Front Mol Neurosci. 2017;10:359.","journal-title":"Front Mol Neurosci"},{"key":"320_CR40","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12915-014-0095-z","volume":"12","author":"J Yang","year":"2014","unstructured":"Yang J, Tang Y, Liu H, Guo F, Ni J, Le W. Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells. BMC Biol. 2014;12:95.","journal-title":"BMC Biol"},{"key":"320_CR41","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/cdd.2013.159","volume":"21","author":"Y Tang","year":"2014","unstructured":"Tang Y, Li T, Li J, Yang J, Liu H, Zhang XJ, et al. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson\u2019s disease. Cell Death Differ. 2014;21:369\u201380.","journal-title":"Cell Death Differ"},{"key":"320_CR42","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1242\/dev.092163","volume":"143","author":"G Masserdotti","year":"2016","unstructured":"Masserdotti G, Gascon S, Gotz M. Direct neuronal reprogramming: learning from and for development. Development. 2016;143:2494\u2013510.","journal-title":"Development"},{"key":"320_CR43","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/s41586-020-2388-4","volume":"582","author":"H Qian","year":"2020","unstructured":"Qian H, Kang X, Hu J, Zhang D, Liang Z, Meng F, et al. Reversing a model of Parkinson\u2019s disease with in situ converted nigral neurons. Nature. 2020;582:550\u20136.","journal-title":"Nature"},{"key":"320_CR44","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.cell.2012.11.045","volume":"152","author":"Y Xue","year":"2013","unstructured":"Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H, Li H, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell. 2013;152:82\u201396.","journal-title":"Cell"},{"key":"320_CR45","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/nature08139","volume":"460","author":"AS Yoo","year":"2009","unstructured":"Yoo AS, Staahl BT, Chen L, Crabtree GR. MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature. 2009;460:642\u20136.","journal-title":"Nature"},{"issue":"332\u2013348","key":"320_CR46","first-page":"e9","volume":"21","author":"DG Abernathy","year":"2017","unstructured":"Abernathy DG, Kim WK, McCoy MJ, Lake AM, Ouwenga R, Lee SW, et al. MicroRNAs induce a permissive chromatin environment that enables neuronal subtype-specific reprogramming of adult human fibroblasts. Cell Stem Cell. 2017;21(332\u2013348):e9.","journal-title":"Cell Stem Cell"},{"key":"320_CR47","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.molcel.2007.07.015","volume":"27","author":"EV Makeyev","year":"2007","unstructured":"Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell. 2007;27:435\u201348.","journal-title":"Mol Cell"},{"key":"320_CR48","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.stemcr.2014.05.020","volume":"3","author":"S Chanda","year":"2014","unstructured":"Chanda S, Ang CE, Davila J, Pak C, Mall M, Lee QY, et al. Generation of induced neuronal cells by the single reprogramming factor ASCL1. Stem Cell Reports. 2014;3:282\u201396.","journal-title":"Stem Cell Reports"},{"key":"320_CR49","doi-asserted-by":"publisher","first-page":"107521","DOI":"10.1016\/j.celrep.2020.03.085","volume":"31","author":"K Zhang","year":"2020","unstructured":"Zhang K, Yu F, Zhu J, Han S, Chen J, Wu X, et al. Imbalance of excitatory\/inhibitory neuron differentiation in neurodevelopmental disorders with an NR2F1 point mutation. Cell Rep. 2020;31:107521.","journal-title":"Cell Rep"},{"key":"320_CR50","doi-asserted-by":"publisher","first-page":"E1234","DOI":"10.1073\/pnas.1611473114","volume":"114","author":"A Faedo","year":"2017","unstructured":"Faedo A, Laporta A, Segnali A, Galimberti M, Besusso D, Cesana E, et al. Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1. Proc Natl Acad Sci U S A. 2017;114:E1234\u201342.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"320_CR51","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1016\/j.stemcr.2021.08.006","volume":"16","author":"T Allison","year":"2021","unstructured":"Allison T, Langerman J, Sabri S, Otero-Garcia M, Lund A, Huang J, et al. Defining the nature of human pluripotent stem cell-derived interneurons via single-cell analysis. Stem Cell Reports. 2021;16:2548\u201364.","journal-title":"Stem Cell Reports"},{"key":"320_CR52","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1126\/science.1059581","volume":"293","author":"C Zuccato","year":"2001","unstructured":"Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington\u2019s disease. Science. 2001;293:493\u20138.","journal-title":"Science"},{"key":"320_CR53","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/ng1219","volume":"35","author":"C Zuccato","year":"2003","unstructured":"Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, et al. Huntingtin interacts with REST\/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 2003;35:76\u201383.","journal-title":"Nat Genet"},{"key":"320_CR54","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.pneurobio.2007.01.003","volume":"81","author":"C Zuccato","year":"2007","unstructured":"Zuccato C, Cattaneo E. Role of brain-derived neurotrophic factor in Huntington\u2019s disease. Prog Neurobiol. 2007;81:294\u2013330.","journal-title":"Prog Neurobiol"},{"key":"320_CR55","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1111\/j.1750-3639.2007.00111.x","volume":"18","author":"C Zuccato","year":"2008","unstructured":"Zuccato C, Marullo M, Conforti P, MacDonald ME, Tartari M, Cattaneo E. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington\u2019s disease. Brain Pathol. 2008;18:225\u201338.","journal-title":"Brain Pathol"},{"key":"320_CR56","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nbt.1529","volume":"27","author":"SM Chambers","year":"2009","unstructured":"Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009;27:275\u201380.","journal-title":"Nat Biotechnol"},{"key":"320_CR57","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1093\/hmg\/ddv080","volume":"24","author":"VB Mattis","year":"2015","unstructured":"Mattis VB, Tom C, Akimov S, Saeedian J, Ostergaard ME, Southwell AL, et al. HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity. Hum Mol Genet. 2015;24:3257\u201371.","journal-title":"Hum Mol Genet"},{"issue":"48\u201357","key":"320_CR58","first-page":"e4","volume":"94","author":"F Gasset-Rosa","year":"2017","unstructured":"Gasset-Rosa F, Chillon-Marinas C, Goginashvili A, Atwal RS, Artates JW, Tabet R, et al. Polyglutamine-expanded huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport. Neuron. 2017;94(48\u201357):e4.","journal-title":"Neuron"},{"issue":"93\u2013107","key":"320_CR59","first-page":"e6","volume":"94","author":"JC Grima","year":"2017","unstructured":"Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, et al. Mutant Huntingtin disrupts the nuclear pore complex. Neuron. 2017;94(93\u2013107):e6.","journal-title":"Neuron"},{"key":"320_CR60","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1097\/WNR.0b013e32832e34ee","volume":"20","author":"A Silvestroni","year":"2009","unstructured":"Silvestroni A, Faull RL, Strand AD, Moller T. Distinct neuroinflammatory profile in post-mortem human Huntington\u2019s disease. NeuroReport. 2009;20:1098\u2013103.","journal-title":"NeuroReport"},{"key":"320_CR61","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.neuron.2014.05.032","volume":"83","author":"JL Plotkin","year":"2014","unstructured":"Plotkin JL, Day M, Peterson JD, Xie Z, Kress GJ, Rafalovich I, et al. Impaired TrkB receptor signaling underlies corticostriatal dysfunction in Huntington\u2019s disease. Neuron. 2014;83:178\u201388.","journal-title":"Neuron"},{"key":"320_CR62","doi-asserted-by":"publisher","first-page":"268ra178","DOI":"10.1126\/scitranslmed.3010523","volume":"6","author":"XH Lu","year":"2014","unstructured":"Lu XH, Mattis VB, Wang N, Al-Ramahi I, van den Berg N, Fratantoni SA, et al. Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington\u2019s disease. Sci Transl Med. 2014;6:268ra178.","journal-title":"Sci Transl Med"},{"key":"320_CR63","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.stemcr.2017.01.022","volume":"8","author":"X Xu","year":"2017","unstructured":"Xu X, Tay Y, Sim B, Yoon SI, Huang Y, Ooi J, et al. Reversal of phenotypic abnormalities by CRISPR\/Cas9-mediated gene correction in huntington disease patient-derived induced pluripotent Stem Cells. Stem Cell Reports. 2017;8:619\u201333.","journal-title":"Stem Cell Reports"},{"key":"320_CR64","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1093\/hmg\/ddab200","volume":"30","author":"SS Akimov","year":"2021","unstructured":"Akimov SS, Jiang M, Kedaigle AJ, Arbez N, Marque LO, Eddings CR, et al. Immortalized striatal precursor neurons from Huntington\u2019s disease patient-derived iPS cells as a platform for target identification and screening for experimental therapeutics. Hum Mol Genet. 2021;30:2469\u201387.","journal-title":"Hum Mol Genet"},{"key":"320_CR65","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.stem.2013.11.006","volume":"13","author":"JD Miller","year":"2013","unstructured":"Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, et al. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell. 2013;13:691\u2013705.","journal-title":"Cell Stem Cell"},{"key":"320_CR66","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41593-017-0066-0","volume":"21","author":"N Li","year":"2018","unstructured":"Li N, Lagier-Tourenne C. Nuclear pores: the gate to neurodegeneration. Nat Neurosci. 2018;21:156\u20138.","journal-title":"Nat Neurosci"},{"key":"320_CR67","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41571-020-00442-4","volume":"18","author":"AS Azmi","year":"2021","unstructured":"Azmi AS, Uddin MH, Mohammad RM. The nuclear export protein XPO1 - from biology to targeted therapy. Nat Rev Clin Oncol. 2021;18:152\u201369.","journal-title":"Nat Rev Clin Oncol"},{"key":"320_CR68","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1016\/j.celrep.2016.07.035","volume":"16","author":"AX Sun","year":"2016","unstructured":"Sun AX, Yuan Q, Tan S, Xiao Y, Wang D, Khoo AT, et al. Direct induction and functional maturation of forebrain GABAergic neurons from human pluripotent stem cells. Cell Rep. 2016;16:1942\u201353.","journal-title":"Cell Rep"},{"key":"320_CR69","doi-asserted-by":"publisher","first-page":"5121","DOI":"10.1038\/s41467-021-25460-3","volume":"12","author":"ACW Smith","year":"2021","unstructured":"Smith ACW, Jonkman S, Difeliceantonio AG, O\u2019Connor RM, Ghoshal S, Romano MF, et al. Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions. Nat Commun. 2021;12:5121.","journal-title":"Nat Commun"},{"key":"320_CR70","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1016\/j.celrep.2016.06.090","volume":"16","author":"Q Zhang","year":"2016","unstructured":"Zhang Q, Zhang Y, Wang C, Xu Z, Liang Q, An L, et al. The Zinc finger transcription factor Sp9 is required for the development of striatopallidal projection neurons. Cell Rep. 2016;16:1431\u201344.","journal-title":"Cell Rep"},{"key":"320_CR71","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1126\/science.aad2033","volume":"351","author":"AC Woerner","year":"2016","unstructured":"Woerner AC, Frottin F, Hornburg D, Feng LR, Meissner F, Patra M, et al. Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science. 2016;351:173\u20136.","journal-title":"Science"},{"issue":"925\u2013940","key":"320_CR72","first-page":"e7","volume":"99","author":"B Eftekharzadeh","year":"2018","unstructured":"Eftekharzadeh B, Daigle JG, Kapinos LE, Coyne A, Schiantarelli J, Carlomagno Y, et al. Tau Protein disrupts nucleocytoplasmic transport in Alzheimer\u2019s disease. Neuron. 2018;99(925\u2013940):e7.","journal-title":"Neuron"},{"key":"320_CR73","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1038\/s41593-021-00859-9","volume":"24","author":"YC Lin","year":"2021","unstructured":"Lin YC, Kumar MS, Ramesh N, Anderson EN, Nguyen AT, Kim B, et al. Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway. Nat Neurosci. 2021;24:1077\u201388.","journal-title":"Nat Neurosci"},{"key":"320_CR74","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature14973","volume":"525","author":"K Zhang","year":"2015","unstructured":"Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, et al. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature. 2015;525:56\u201361.","journal-title":"Nature"},{"key":"320_CR75","doi-asserted-by":"publisher","first-page":"10428","DOI":"10.1073\/pnas.0401424101","volume":"101","author":"L Vergnes","year":"2004","unstructured":"Vergnes L, Peterfy M, Bergo MO, Young SG, Reue K. Lamin B1 is required for mouse development and nuclear integrity. Proc Natl Acad Sci U S A. 2004;101:10428\u201333.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"320_CR76","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1091\/mbc.E15-05-0307","volume":"27","author":"C Giacomini","year":"2016","unstructured":"Giacomini C, Mahajani S, Ruffilli R, Marotta R, Gasparini L. Lamin B1 protein is required for dendrite development in primary mouse cortical neurons. Mol Biol Cell. 2016;27:35\u201347.","journal-title":"Mol Biol Cell"},{"key":"320_CR77","doi-asserted-by":"publisher","first-page":"15098","DOI":"10.1038\/ncomms15098","volume":"8","author":"CM Gigante","year":"2017","unstructured":"Gigante CM, Dibattista M, Dong FN, Zheng X, Yue S, Young SG, et al. Lamin B1 is required for mature neuron-specific gene expression during olfactory sensory neuron differentiation. Nat Commun. 2017;8:15098.","journal-title":"Nat Commun"},{"key":"320_CR78","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/s41436-020-00980-3","volume":"23","author":"DA Parry","year":"2021","unstructured":"Parry DA, Martin CA, Greene P, Marsh JA, Genomics England Research C, Blyth M, et al. Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy. Genet Med. 2021;23:408\u201314.","journal-title":"Genet Med"},{"key":"320_CR79","doi-asserted-by":"publisher","first-page":"e105819","DOI":"10.15252\/embj.2020105819","volume":"40","author":"TA Bedrosian","year":"2021","unstructured":"Bedrosian TA, Houtman J, Eguiguren JS, Ghassemzadeh S, Rund N, Novaresi NM, et al. Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis. EMBO J. 2021;40:e105819.","journal-title":"EMBO J"},{"key":"320_CR80","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1101\/gad.217281.113","volume":"27","author":"M Sadaie","year":"2013","unstructured":"Sadaie M, Salama R, Carroll T, Tomimatsu K, Chandra T, Young AR, et al. Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence. Genes Dev. 2013;27:1800\u20138.","journal-title":"Genes Dev"},{"key":"320_CR81","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13059-020-02003-5","volume":"21","author":"N Briand","year":"2020","unstructured":"Briand N, Collas P. Lamina-associated domains: peripheral matters and internal affairs. Genome Biol. 2020;21:85.","journal-title":"Genome Biol"},{"key":"320_CR82","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/nature11557","volume":"491","author":"GH Liu","year":"2012","unstructured":"Liu GH, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, et al. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature. 2012;491:603\u20137.","journal-title":"Nature"},{"key":"320_CR83","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1091\/mbc.e11-10-0884","volume":"23","author":"A Freund","year":"2012","unstructured":"Freund A, Laberge RM, Demaria M, Campisi J. Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell. 2012;23:2066\u201375.","journal-title":"Mol Biol Cell"},{"key":"320_CR84","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1523\/JNEUROSCI.2507-20.2020","volume":"41","author":"B Ding","year":"2021","unstructured":"Ding B, Tang Y, Ma S, Akter M, Liu ML, Zang T, et al. Disease modeling with human neurons reveals LMNB1 dysregulation underlying DYT1 dystonia. J Neurosci. 2021;41:2024\u201338.","journal-title":"J Neurosci"},{"key":"320_CR85","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/j.celrep.2016.09.062","volume":"17","author":"E Vera","year":"2016","unstructured":"Vera E, Bosco N, Studer L. Generating late-onset human iPSC-based disease models by inducing neuronal age-related phenotypes through telomerase manipulation. Cell Rep. 2016;17:1184\u201392.","journal-title":"Cell Rep"}],"container-title":["Inflammation and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41232-024-00320-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41232-024-00320-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41232-024-00320-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:08:15Z","timestamp":1708301295000},"score":1,"resource":{"primary":{"URL":"https:\/\/inflammregen.biomedcentral.com\/articles\/10.1186\/s41232-024-00320-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["320"],"URL":"https:\/\/doi.org\/10.1186\/s41232-024-00320-x","relation":{},"ISSN":["1880-8190"],"issn-type":[{"value":"1880-8190","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]},"assertion":[{"value":"30 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All of the authors have reviewed and approved the final version of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7"}}