title: The genomic and transcriptomic landscape of a HeLa cell line.
abstract: HeLa is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using HeLa cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a HeLa cell line. We performed DNA and RNA sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the HeLa gene expression profile revealed that several pathways, including cell cycle and DNA repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments, and has implications for the use of HeLa as a model of human biology.
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany.
authors.forename: Jonathan J M
authors.initials: JJ
authors.lastname: Landry
authors.forename: Paul Theodor
authors.initials: PT
authors.lastname: Pyl
authors.forename: Tobias
authors.initials: T
authors.lastname: Rausch
authors.forename: Thomas
authors.initials: T
authors.lastname: Zichner
authors.forename: Manu M
authors.initials: MM
authors.lastname: Tekkedil
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Stütz
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Raeka S
authors.initials: RS
authors.lastname: Aiyar
authors.forename: Gregoire
authors.initials: G
authors.lastname: Pau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delhomme
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
authors.forename: Jan O
authors.initials: JO
authors.lastname: Korbel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
mesh_terms: D000483:Alleles; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D005787:Gene Frequency; D015894:Genome, Human; D023281:Genomics; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D059467:Transcriptome
keywords: HeLa cell line; genomics; resource; transcriptomics; variation
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