%0 Generic
%A Landry, Jonathan
%D 2012
%F heidok:14617
%R 10.11588/heidok.00014617
%T The genomic and transcriptomic landscape of HeLa cells
%U https://archiv.ub.uni-heidelberg.de/volltextserver/14617/
%X HeLa is and always has been the most widely used model cell line for studying human cellular and molecular biology, and has thus defined our current understanding of human cells. However, no genomic or transcriptomic references exist for this cell line, and studies thus far have relied on the undoubtedly different human reference genome. This knowledge is essential to guide the increasing number of molecular and genetic studies being done in this cell line, both for design and interpretation. During my doctoral work, I performed deep DNA and RNA sequencing of a HeLa-Kyoto cell line and analyzed its mutational portfolio and gene expression profile. We generated a comprehensive description of the genomic and transcriptomic landscape of this cell line. A segmentation of the genome according to copy number revealed an astonishingly high level of aneuploidy and numerous large structural variations at unprecedented resolution. Remnants of catastrophic chromosome shattering, known as chromothripsis, were evident. Comparison of the HeLa expression profile to the physiological range of human gene expression reveals that several pathways, including cell cycle and DNA repair mechanisms, are 'abnormally' expressed. These results provide the first detailed account of the extent of variations in the HeLa genome, yielding insight into their impact on gene expression, cellular function, and their origins during the evolution of this cell line. This study demonstrates the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments. The important resources provided will help to reevaluate the way HeLa is used to model human biology.
%Z The content of this thesis is available in Landry et al., G3 2013:    http://g3journal.org/content/3/8/1213    The genome sequence described in this thesis was derived from a HeLa cell line. Henrietta Lacks, and the HeLa cell line that was established from her tumor cells in 1951, have made significant contributions to scientific progress and advances in human health. We are grateful to Henrietta Lacks, now deceased, and to her surviving family members for their contributions to biomedical research.    Please consult the publication.  For additional requests please contact the EMBL press office:  pressoffice@embl.de