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Optical Genome Mapping Reveals Genomic Alterations upon Gene Editing in hiPSCs: Implications for Neural Tissue Differentiation and Brain Organoid Research.
Gallego Villarejo, Lucia; Gerding, Wanda M; Bachmann, Lisa; Hardt, Luzie H I; Bormann, Stefan; Nguyen, Huu Phuc; Müller, Thorsten.
Afiliação
  • Gallego Villarejo L; Department of Molecular Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
  • Gerding WM; Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44801 Bochum, Germany.
  • Bachmann L; International Graduate School of Neuroscience, Ruhr-University Bochum, 44801 Bochum, Germany.
  • Hardt LHI; Department of Human Genetics, Ruhr-University Bochum, 44801 Bochum, Germany.
  • Bormann S; Department of Molecular Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
  • Nguyen HP; Department of Molecular Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
  • Müller T; Department of Molecular Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
Cells ; 13(6)2024 Mar 14.
Article em En | MEDLINE | ID: mdl-38534351
ABSTRACT
Genome editing, notably CRISPR (cluster regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), has revolutionized genetic engineering allowing for precise targeted modifications. This technique's combination with human induced pluripotent stem cells (hiPSCs) is a particularly valuable tool in cerebral organoid (CO) research. In this study, CRISPR/Cas9-generated fluorescently labeled hiPSCs exhibited no significant morphological or growth rate differences compared with unedited controls. However, genomic aberrations during gene editing necessitate efficient genome integrity assessment methods. Optical genome mapping, a high-resolution genome-wide technique, revealed genomic alterations, including chromosomal copy number gain and losses affecting numerous genes. Despite these genomic alterations, hiPSCs retain their pluripotency and capacity to generate COs without major phenotypic changes but one edited cell line showed potential neuroectodermal differentiation impairment. Thus, this study highlights optical genome mapping in assessing genome integrity in CRISPR/Cas9-edited hiPSCs emphasizing the need for comprehensive integration of genomic and morphological analysis to ensure the robustness of hiPSC-based models in cerebral organoid research.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes Induzidas / Edição de Genes Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes Induzidas / Edição de Genes Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article