{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:57:09Z","timestamp":1779364629864,"version":"3.53.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"24","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Hopkins Post-baccalaureate Research Education Program","award":["R01 NS089076"],"award-info":[{"award-number":["R01 NS089076"]}]},{"name":"Hopkins Post-baccalaureate Research Education Program","award":["NIH R25GM109441"],"award-info":[{"award-number":["NIH R25GM109441"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM008334"],"award-info":[{"award-number":["T32 GM008334"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS104320-01A1"],"award-info":[{"award-number":["R21NS104320-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS083365"],"award-info":[{"award-number":["R21NS083365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have previously established induced pluripotent stem cell (iPSC) models of Huntington\u2019s disease (HD), demonstrating CAG-repeat-expansion-dependent cell biological changes and toxicity. However, the current differentiation protocols are cumbersome and time consuming, making preparation of large quantities of cells for biochemical or screening assays difficult. Here, we report the generation of immortalized striatal precursor neurons (ISPNs) with normal (33) and expanded (180) CAG repeats from HD iPSCs, differentiated to a phenotype resembling medium spiny neurons (MSN), as a proof of principle for a more tractable patient-derived cell model. For immortalization, we used co-expression of the enzymatic component of telomerase hTERT and conditional expression of c-Myc. ISPNs can be propagated as stable adherent cell lines, and rapidly differentiated into highly homogeneous MSN-like cultures within 2 weeks, as demonstrated by immunocytochemical criteria. Differentiated ISPNs recapitulate major HD-related phenotypes of the parental iPSC model, including brain-derived neurotrophic factor (BDNF)-withdrawal-induced cell death that can be rescued by small molecules previously validated in the parental iPSC model. Proteome and RNA-seq analyses demonstrate separation of HD versus control samples by principal component analysis. We identified several networks, pathways, and upstream regulators, also found altered in HD iPSCs, other HD models, and HD patient samples. HD ISPN lines may be useful for studying HD-related cellular pathogenesis, and for use as a platform for HD target identification and screening experimental therapeutics. The described approach for generation of ISPNs from differentiated patient-derived iPSCs could be applied to a larger allelic series of HD cell lines, and to comparable modeling of other genetic disorders.<\/jats:p>","DOI":"10.1093\/hmg\/ddab200","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T19:11:12Z","timestamp":1626462672000},"page":"2469-2487","source":"Crossref","is-referenced-by-count":15,"title":["Immortalized striatal precursor neurons from Huntington\u2019s disease patient-derived iPS cells as a platform for target identification and screening for experimental therapeutics"],"prefix":"10.1093","volume":"30","author":[{"given":"Sergey S","family":"Akimov","sequence":"first","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mali","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-5046","authenticated-orcid":false,"given":"Amanda J","family":"Kedaigle","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Computational and Systems Biology Graduate Program, Massachusetts Institute of Technology, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Arbez","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard O","family":"Marque","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsy R","family":"Eddings","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T","family":"Ranum","sequence":"additional","affiliation":[{"name":"The Department of Pathology and Laboratory Medicine, The University of Pennsylvania, The Raymond G Perelman Center for Cellular and Molecular Therapeutics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Whelan","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren R","family":"DeVine","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Conover C","family":"Talbot","sequence":"additional","affiliation":[{"name":"The Johns Hopkins School of Medicine, Institute for Basic Biomedical Sciences, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N","family":"Cole","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-5644","authenticated-orcid":false,"given":"Tamara","family":"Ratovitski","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly L","family":"Davidson","sequence":"additional","affiliation":[{"name":"The Department of Pathology and Laboratory Medicine, The University of Pennsylvania, The Raymond G Perelman Center for Cellular and Molecular Therapeutics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"The Department of Pathology and Laboratory Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Computational and Systems Biology Graduate Program, Massachusetts Institute of Technology, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"},{"name":"Department of Neurology, Neuroscience and Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"2021120506365503200_ref1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington's disease: from molecular pathogenesis to clinical treatment","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"2021120506365503200_ref2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrneurol.2014.24","article-title":"Huntington disease: natural history, biomarkers and prospects for therapeutics","volume":"10","author":"Ross","year":"2014","journal-title":"Nat. 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