Characterization of structural variants in KOLF2.1J iPSCs and their potential impact on forebrain organoid differentiation
Year: 2026
Type: article
Abstract: The KOLF2.1J human induced pluripotent stem cell (iPSC) line was created as a reference for neurological disease modeling. Previous genotyping efforts identified several large structural variants (SVs), raising questions about their potential impact on neuronal differentiation. Here, we identified 37 additional SVs using long-read sequencing and optical genome mapping. Additionally, we found that one of the known SVs contained a previously undetected overlap with RYBP, a neurodevelopmental gene. To assess the functional consequences of these SVs, we performed single-cell RNA sequencing of day 90 forebrain organoids derived from KOLF2.1J and two independent control iPSC lines. While cell-type composition was preserved, multiple SV-affected genes were differentially expressed and cell-cell adhesion and synapse-related processes were enriched in KOLF2.1J organoids. These findings highlight the importance of robust genetic characterization and multi-line validation for reliable iPSC-based modeling.
Source: Stem Cell Reports
Institutions: Karlsruhe Institute of Technology, Heidelberg Academy of Sciences and Humanities, Hertie Institute for Clinical Brain Research, University of Tübingen, Stanford Medicine, Stanford University, The Jackson Laboratory for Genomic Medicine, Bernstein Center for Computational Neuroscience Tübingen, University of Connecticut, UConn Health
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Brain and Behavior Research Foundation, Jackson Laboratory, Heidelberger Akademie der Wissenschaften, University of Connecticut Health Center, Deutsche Forschungsgemeinschaft, Daimler und Benz Stiftung, Gemeinnützige Hertie-Stiftung, Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
OpenAlex ID: W7221007000