title: Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells.
abstract: Characterization of the transcriptional regulatory network of the normal cell cycle is essential for understanding the perturbations that lead to cancer. However, the complete set of cycling genes in primary cells has not yet been identified. Here, we report the results of genome-wide expression profiling experiments on synchronized primary human foreskin fibroblasts across the cell cycle. Using a combined experimental and computational approach to deconvolve measured expression values into "single-cell" expression profiles, we were able to overcome the limitations inherent in synchronizing nontransformed mammalian cells. This allowed us to identify 480 periodically expressed genes in primary human foreskin fibroblasts. Analysis of the reconstructed primary cell profiles and comparison with published expression datasets from synchronized transformed cells reveals a large number of genes that cycle exclusively in primary cells. This conclusion was supported by both bioinformatic analysis and experiments performed on other cell types. We suggest that this approach will help pinpoint genetic elements contributing to normal cell growth and cellular transformation.
authors.affiliation: Department of Computer Science, School of Computer Science and Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA. zivbj@cs.cmu.edu
authors.forename: Ziv
authors.initials: Z
authors.lastname: Bar-Joseph
authors.forename: Zahava
authors.initials: Z
authors.lastname: Siegfried
authors.forename: Michael
authors.initials: M
authors.lastname: Brandeis
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dynlacht
authors.forename: Itamar
authors.initials: I
authors.lastname: Simon
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000145:classification / Q000235:genetics*; D002478:Cells, Cultured; D019295:Computational Biology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006262:Health; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins