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Therefore, we asked whether genetic modification of hiPSC\u2010NSCs exacerbates chromosomal abnormalities that may occur during passaging and whether they may cause any functional perturbations in NSCs in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The transgenic cassette was inserted into the AAVS1 locus, and the genetic integrity of zinc\u2010finger nuclease (ZFN)\u2010modified hiPSC\u2010NSCs was assessed by the SNP\u2010based karyotyping. The hiPSC\u2010NSC proliferation was assessed in vitro by the EdU incorporation assay and in vivo by staining of brain slices with Ki\u201067 antibody at 2 and 8\u00a0weeks after transplantation of ZFN\u2010NSCs with and without chromosomal aberration into the striatum of immunodeficient rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During early passages, no chromosomal abnormalities were detected in unmodified or ZFN\u2010modified hiPSC\u2010NSCs. However, at higher passages both cell populations acquired duplication of the entire long arm of chromosome 1, dup(1)q. ZNF\u2010NSCs carrying dup(1)q exhibited higher proliferation rate than karyotypically intact cells, which was partly mediated by increased expression of <jats:italic>AKT3<\/jats:italic> located on Chr1q. Compared to karyotypically normal ZNF\u2010NSCs, cells with dup(1)q also exhibited increased proliferation in vivo 2\u00a0weeks, but not 2\u00a0months, after transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results demonstrate that, independently of ZFN\u2010editing, hiPSC\u2010NSCs have a propensity for acquiring dup(1)q and this aberration results in increased proliferation which might compromise downstream hiPSC\u2010NSC applications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12892","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T07:50:18Z","timestamp":1600069818000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Acquisition of chromosome 1q duplication in parental and genome\u2010edited human\u2010induced pluripotent stem cell\u2010derived neural stem cells results in their higher proliferation rate in vitro and in vivo"],"prefix":"10.1111","volume":"53","author":[{"given":"Narges Zare","family":"Mehrjardi","sequence":"first","affiliation":[{"name":"Center for Physiology and Pathophysiology Institute for Neurophysiology Medical Faculty University of Cologne Cologne Germany"},{"name":"Department of Stem Cells and Developmental Biology Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Molcanyi","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pathophysiology Institute for Neurophysiology Medical Faculty University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firuze Fulya","family":"Hatay","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pathophysiology Institute for Neurophysiology Medical Faculty University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Timmer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University Hospital Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebrahim","family":"Shahbazi","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Developmental Biology Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus P.","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Herms","sequence":"additional","affiliation":[{"name":"Department of Genomics, Life &amp; Brain Center Institute for Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Biomedicine Medical Genetics Research Group Genomics University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Heilmann\u2010Heimbach","sequence":"additional","affiliation":[{"name":"Department of Genomics, Life &amp; Brain Center Institute for Human Genetics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Wunderlich","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne University of Cologne Cologne Germany"},{"name":"Max Planck Institute for Metabolism Research and Institute for Genetics, University of Cologne Cologne Germany"},{"name":"Cologne Cluster of Excellence in Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Prochnow","sequence":"additional","affiliation":[{"name":"Clinic for Neurology St. Josef\u2010Hospital Clinic of the Ruhr\u2010University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiden","family":"Haghikia","sequence":"additional","affiliation":[{"name":"Clinic for Neurology St. Josef\u2010Hospital Clinic of the Ruhr\u2010University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Lampert","sequence":"additional","affiliation":[{"name":"Institute of Physiology Uniklinik, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Hescheler","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pathophysiology Institute for Neurophysiology Medical Faculty University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund A. 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