{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:50:21Z","timestamp":1783540221603,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["16-15-10128"],"award-info":[{"award-number":["16-15-10128"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a severe neurodegenerative disorder caused by a CAG triplet expansion in the first exon of the HTT gene. Here we report the introduction of an HD mutation into the genome of healthy human embryonic fibroblasts through CRISPR\/Cas9-mediated homologous recombination. We verified the specificity of the created HTT-editing system and confirmed the absence of undesirable genomic modifications at off-target sites. We showed that both mutant and control isogenic induced pluripotent stem cells (iPSCs) derived by reprogramming of the fibroblast clones can be differentiated into striatal medium spiny neurons. We next demonstrated phenotypic abnormalities in the mutant iPSC-derived neural cells, including impaired neural rosette formation and increased sensitivity to growth factor withdrawal. Moreover, using electron microscopic analysis, we detected a series of ultrastructural defects in the mutant neurons, which did not contain huntingtin aggregates, suggesting that these defects appear early in HD development. Thus, our study describes creation of a new isogenic iPSC-based cell system that models HD and recapitulates HD-specific disturbances in the mutant cells, including some ultrastructural features implemented for the first time.<\/jats:p>","DOI":"10.3390\/jpm10040215","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T10:47:28Z","timestamp":1605005248000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Human Induced Pluripotent Stem Cell-Derived Isogenic Model of Huntington\u2019s Disease Based on Neuronal Cells Has Several Relevant Phenotypic Abnormalities"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-8465","authenticated-orcid":false,"given":"Tuyana","family":"Malankhanova","sequence":"first","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubov","family":"Suldina","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-9108","authenticated-orcid":false,"given":"Elena","family":"Grigor\u2019eva","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-5549","authenticated-orcid":false,"given":"Sergey","family":"Medvedev","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Minina","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3307-8819","authenticated-orcid":false,"given":"Ksenia","family":"Morozova","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kiseleva","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren","family":"Zakian","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1916-1333","authenticated-orcid":false,"given":"Anastasia","family":"Malakhova","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1212\/WNL.0b013e318249f683","article-title":"CAG repeat expansion in Huntington disease determines age at onset in a fully dominant 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