Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells

Ziv Bar-Joseph*, Zahava Siegfried, Michael Brandeis, Benedikt Brors, Yong Lu, Roland Eils, Brian D. Dynlacht, Itamar Simon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

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.

Original languageAmerican English
Pages (from-to)955-960
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number3
DOIs
StatePublished - 22 Jan 2008

Keywords

  • Deconvolution
  • Expression profile

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