ArticleScientific reports2022
Wildtype heterogeneity contributes to clonal variability in genome edited cells.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
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- CRISPR/Cas9-mediated targeted knock-in of human erythropoietin at the β-casein locus results in lactogenic hormone-responsive expression in HC11 mammary epithelial cells.Scientific reports · 2026Article
- Reduced PRC2 function causes asparaginase resistance in T-ALL by decreasing WNT pathway activity.Blood advances · 2026Article
- Functional genomic analysis of non-canonical DNA regulatory elements of the aryl hydrocarbon receptor.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
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- Arp2/3-dependent regulation of ciliogenesis governs adaptive distal tubular epithelial cell states in kidney disease.Science advances · 2025Article
- Functional genomic analysis of non-canonical DNA regulatory elements of the aryl hydrocarbon receptor.bioRxiv : the preprint server for biology · 2025Article
- Posterior Limbal Mesenchymal Stromal Cells Promote Proliferation and Stemness of Transition Zone Cells: A Novel Insight Into Corneal Endothelial Rejuvenation.Investigative ophthalmology & visual science · 2025Article
- AKAP12 Variant 1 Knockout Enhances Vascular Endothelial Cell Motility.Journal of vascular research · 2025Article
- Functional genomics screens reveal a role for TBC1D24 and SV2B in antibody-dependent enhancement of dengue virus infection.Journal of virology · 2024Article
- Characterization, Structure, and Inhibition of the Human Succinyl-CoA:glutarate-CoA Transferase, a Putative Genetic Modifier of Glutaric Aciduria Type 1.ACS chemical biology · 2024Article
- Generation and characterization of inducible KRAB-dCas9 iPSCs from primates for cross-species CRISPRi.iScience · 2024Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Genome editing tools such as CRISPR/Cas9 enable the rapid and precise manipulation of genomes. CRISPR-based genome editing has greatly simplified the study of gene function in cell lines, but its widespread use has also highlighted challenges of reproducibility. Phenotypic variability among different knockout clones of the same gene is a common problem confounding the establishment of robust genotype-phenotype correlations. Optimized genome editing protocols to enhance reproducibility include measures to reduce off-target effects. However, even if current state-of-the-art protocols are applied phenotypic variability is frequently observed. Here we identify heterogeneity of wild-type cells as an important and often neglected confounding factor in genome-editing experiments. We demonstrate that isolation of individual wild-type clones from an apparently homogenous stable cell line uncovers significant phenotypic differences between clones. Strikingly, we observe hundreds of differentially regulated transcripts (477 up- and 306 downregulated) when comparing two populations of wild-type cells. Furthermore, we show a variety of cellular and biochemical alterations in different wild-type clones in a range that is commonly interpreted as biologically relevant in genome-edited cells. Heterogeneity of wild-type cells thus contributes to variability in genome-edited cells when these are generated through isolation of clones. We show that the generation of monoclonal isogenic wild-type cells prior to genomic manipulation reduces phenotypic variability. We therefore propose to generate matched isogenic control cells prior to genome editing to increase reproducibility.
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