2019
DOI: 10.1038/s41598-019-40897-9
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Extensive epigenetic and transcriptomic variability between genetically identical human B-lymphoblastoid cells with implications in pharmacogenomics research

Abstract: Genotyped human B-lymphoblastoid cell lines (LCLs) are widely used models in mapping quantitative trait loci for chromatin features, gene expression, and drug response. The extent of genotype-independent functional genomic variability of the LCL model, although largely overlooked, may inform association study design. In this study, we use flow cytometry, chromatin immunoprecipitation sequencing and mRNA sequencing to study surface marker patterns, quantify genome-wide chromatin changes (H3K27ac) and transcript… Show more

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Cited by 21 publications
(29 citation statements)
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“…Mechanistically, a portion of this variance is expected to arise from heritable yet transient epigenetic signatures ( Shaffer et al, 2020 ). Indeed, epigenetic diversity affecting chromatic architecture across LCL subclones from a single donor was recently demonstrated through ChIP-Seq analysis ( Ozgyin et al, 2019 ). Lastly, as a principle of evolution, phenotypic differences do not necessarily have to be selected directly; they may simply be carried over in cells possessing other selected features.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Mechanistically, a portion of this variance is expected to arise from heritable yet transient epigenetic signatures ( Shaffer et al, 2020 ). Indeed, epigenetic diversity affecting chromatic architecture across LCL subclones from a single donor was recently demonstrated through ChIP-Seq analysis ( Ozgyin et al, 2019 ). Lastly, as a principle of evolution, phenotypic differences do not necessarily have to be selected directly; they may simply be carried over in cells possessing other selected features.…”
Section: Discussionmentioning
confidence: 99%
“…84 Indeed, epigenetic diversity affecting chromatic architecture across LCL subclones from a single donor was recently demonstrated through ChIP-Seq analysis. 85 Lastly, as a principle of evolution, phenotypic differences do not necessarily have to be selected directly; they may simply be carried over in cells possessing other selected features. With respect to the stochastic model presented herein, the simulated phenotype advantage of classswitched memory vs. non-switched memory cells need not be construed as originating from heavy chain isotype expression.…”
Section: Viral Origins Of Lcl Phenotypic Variancementioning
confidence: 99%
“…The increase in variability for recently evolved enhancers was not due to major differences in H3K27ac enrichment at recently evolved elements, as the relationship between variability and H3K27ac enrichment for gains and new enhancers was not significantly different from stable enhancers or enhancers in general (p = 0.2, Figure S3C). We also found no indication that line to line variability was a factor in our analysis as flagging enhancers that were variable between 5 independent LCL lines from the same individual (Ozgyin et al, 2019) did not affect our observations (Figure S3D). In addition, we found no indication that variability of enhancers that were evolutionary new was linked to differences in ancestry between the individuals analyzed (see STAR Methods; Figures S3E-S3H).…”
Section: Recently Evolved Regulatory Dna Is Predominantly Variable Between Individualsmentioning
confidence: 70%
“…Line to line variability was determined using H3K27ac data generated in 5 independent cell lines that were obtained from a single individual (Ozgyin et al, 2019). H3K27ac data was obtainted and mapped to the human genome (hg38) as described above.…”
Section: Analysis Of Line To Line Variabilitymentioning
confidence: 99%
“…We also identified a reduction in CI subunit protein abundance, holoenzyme abundance, and CI activity in both HEK293 TAZ-KO cells and BTHS LCLs; however, in BTHS LCLs reduced mRNA expression of CI subunits was not observed. The differences in mRNA expression observed between the HEK293s and the LCLs could be due to epigenetic and transcriptomic differences observed in EBV transformed LCL lines, the genetic differences between the BTHS individuals, and/or cell type specific regulation of CI associated genes/proteins (49). This hypothesis emphasizes the need for a clearer understanding of the cell-specific effects of abnormal CL content.…”
Section: Discussionmentioning
confidence: 99%