Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function

Abstract The Jurkat cell line, derived from a case of T-cell lymphoblastic leukaemia, is widely employed as a model T-cell for biomedical research, including for the preclinical characterisation of cellular therapies such as chimeric antigen receptor T-cells. Here, we characterised genomic, transcri...

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Main Authors: Andrew Wilson, Nathaniel Dasyam, Felix O’Hagan, Dianna Farrell, Claire Turner, Anne Jay, Alfonso Schmidt, Rachel Beddow, Tina Lillis, Tom Chin, Rachel Perret, Michelle McCulley, Robert Weinkove
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-95903-0
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author Andrew Wilson
Nathaniel Dasyam
Felix O’Hagan
Dianna Farrell
Claire Turner
Anne Jay
Alfonso Schmidt
Rachel Beddow
Tina Lillis
Tom Chin
Rachel Perret
Michelle McCulley
Robert Weinkove
author_facet Andrew Wilson
Nathaniel Dasyam
Felix O’Hagan
Dianna Farrell
Claire Turner
Anne Jay
Alfonso Schmidt
Rachel Beddow
Tina Lillis
Tom Chin
Rachel Perret
Michelle McCulley
Robert Weinkove
author_sort Andrew Wilson
collection DOAJ
description Abstract The Jurkat cell line, derived from a case of T-cell lymphoblastic leukaemia, is widely employed as a model T-cell for biomedical research, including for the preclinical characterisation of cellular therapies such as chimeric antigen receptor T-cells. Here, we characterised genomic, transcriptomic, and functional features of Jurkat clone E6-1 cells from three different laboratories and compared these with Jurkat E6-1 cells from the American Type Culture Collection (ATCC). We identified marked karyotypic heterogeneity both between and within Jurkat E6-1 populations, confirmed through chromosomal microarray. Whole exome sequencing of each cell population revealed both shared and unique mutational profiles, and transcriptomic profiles varied markedly between Jurkat E6-1 cell populations. Finally, the Jurkat E6-1 cell populations exhibited substantial variations in immunophenotype and cytokine production, which were consistent with the genotypic and transcriptomic changes observed. In summary, we identify substantial genomic heterogeneity both between and within Jurkat E6-1 cell populations, highlighting the genomic instability of this line. These genomic changes were associated with differences in protein expression and cytokine production that may affect functional assays. Our findings highlight the importance of monitoring cell passage number, characterising cell lines, and replacing cell line stocks to assure the accuracy, reproducibility, and translatability of assays employing Jurkat E6-1 cells.
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spelling doaj-art-856f995279ee4662b1eac7e243aa795b2025-08-20T03:03:37ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-95903-0Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and functionAndrew Wilson0Nathaniel Dasyam1Felix O’Hagan2Dianna Farrell3Claire Turner4Anne Jay5Alfonso Schmidt6Rachel Beddow7Tina Lillis8Tom Chin9Rachel Perret10Michelle McCulley11Robert Weinkove12Department of Pathology and Molecular Medicine, University of Otago WellingtonCancer Immunotherapy Programme, Malaghan Institute of Medical ResearchCancer Immunotherapy Programme, Malaghan Institute of Medical ResearchWellington Regional Genetics LaboratoryWellington Regional Genetics LaboratoryWellington Regional Genetics LaboratoryHugh Green Technology Centre, Malaghan Institute of Medical ResearchWellington Regional Genetics LaboratoryWellington Regional Genetics LaboratoryWellington Regional Genetics LaboratoryCancer Immunotherapy Programme, Malaghan Institute of Medical ResearchDepartment of Pathology and Molecular Medicine, University of Otago WellingtonCancer Immunotherapy Programme, Malaghan Institute of Medical ResearchAbstract The Jurkat cell line, derived from a case of T-cell lymphoblastic leukaemia, is widely employed as a model T-cell for biomedical research, including for the preclinical characterisation of cellular therapies such as chimeric antigen receptor T-cells. Here, we characterised genomic, transcriptomic, and functional features of Jurkat clone E6-1 cells from three different laboratories and compared these with Jurkat E6-1 cells from the American Type Culture Collection (ATCC). We identified marked karyotypic heterogeneity both between and within Jurkat E6-1 populations, confirmed through chromosomal microarray. Whole exome sequencing of each cell population revealed both shared and unique mutational profiles, and transcriptomic profiles varied markedly between Jurkat E6-1 cell populations. Finally, the Jurkat E6-1 cell populations exhibited substantial variations in immunophenotype and cytokine production, which were consistent with the genotypic and transcriptomic changes observed. In summary, we identify substantial genomic heterogeneity both between and within Jurkat E6-1 cell populations, highlighting the genomic instability of this line. These genomic changes were associated with differences in protein expression and cytokine production that may affect functional assays. Our findings highlight the importance of monitoring cell passage number, characterising cell lines, and replacing cell line stocks to assure the accuracy, reproducibility, and translatability of assays employing Jurkat E6-1 cells.https://doi.org/10.1038/s41598-025-95903-0
spellingShingle Andrew Wilson
Nathaniel Dasyam
Felix O’Hagan
Dianna Farrell
Claire Turner
Anne Jay
Alfonso Schmidt
Rachel Beddow
Tina Lillis
Tom Chin
Rachel Perret
Michelle McCulley
Robert Weinkove
Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function
Scientific Reports
title Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function
title_full Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function
title_fullStr Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function
title_full_unstemmed Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function
title_short Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function
title_sort jurkat t cell lines exhibit marked genomic instability affecting karyotype mutational profile gene expression immunophenotype and function
url https://doi.org/10.1038/s41598-025-95903-0
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