RT Journal Article SR Electronic T1 Transcriptional landscape of cell lines and their tissues of origin JF bioRxiv FD Cold Spring Harbor Laboratory SP 082065 DO 10.1101/082065 A1 Camila M. Lopes-Ramos A1 Joseph N. Paulson A1 Cho-Yi Chen A1 Marieke L. Kuijjer A1 Maud Fagny A1 John Platig A1 Abhijeet R. Sonawane A1 Dawn L. DeMeo A1 John Quackenbush A1 Kimberly Glass YR 2016 UL http://biorxiv.org/content/early/2016/10/20/082065.abstract AB Cell lines are an indispensable tool in biomedical research and often used as surrogates for tissues. An important question is how well a cell line’s transcriptional and regulatory processes reflect those of its tissue of origin. We analyzed RNA-Seq data from GTEx for 127 paired Epstein-Barr virus transformed lymphoblastoid cell lines and whole blood samples; and 244 paired fibroblast cell lines and skin biopsies. A combination of gene expression and network analyses shows that while cell lines carry the expression signatures of their primary tissues, albeit at reduced levels, they also exhibit changes in their patterns of transcription factor regulation. Cell cycle genes are over-expressed in cell lines compared to primary tissue, and they have a reduction of repressive transcription factor targeting. Our results provide insight into the expression and regulatory alterations observed in cell lines and suggest that these changes should be considered when using cell lines as models.HighlightsCell lines differ from their source tissues in gene expression and regulationDistinct cell lines share altered patterns of cell cycle regulationCell cycle genes are less strongly targeted by repressive TFs in cell linesCell lines share expression with their source tissue, but at reduced levels