Meta-analysis reveals conserved cell cycle transcriptional network across multiple human cell types

Bruno Giotti,Anagha Joshi,Tom C Freeman

doi:10.1186/s12864-016-3435-2

Abstract

BackgroundCell division is central to the physiology and pathology of all eukaryotic organisms. The molecular machinery underpinning the cell cycle has been studied extensively in a number of species and core aspects of it have been found to be highly conserved. Similarly, the transcriptional changes associated with this pathway have been studied in different organisms and different cell types. In each case hundreds of genes have been reported to be regulated, however there seems to be little consensus in the genes identified across different studies. In a recent comparison of transcriptomic studies of the cell cycle in different human cell types, only 96 cell cycle genes were reported to be the same across all studies examined.ResultsHere we perform a systematic re-examination of published human cell cycle expression data by using a network-based approach to identify groups of genes with a similar expression profile and therefore function. Two clusters in particular, containing 298 transcripts, showed patterns of expression consistent with cell cycle occurrence across the four human cell types assessed.ConclusionsOur analysis shows that there is a far greater conservation of cell cycle-associated gene expression across human cell types than reported previously, which can be separated into two distinct transcriptional networks associated with the G1/S-S and G2-M phases of the cell cycle. This work also highlights the benefits of performing a re-analysis on combined datasets.

Highlights

Cell division is central to the physiology and pathology of all eukaryotic organisms
As for yeast data, data interpretation is the primary reason for the discrepancies between previous results in defining a cell cycle gene set and that, contrary to what has been reported, the transcriptional network associated with the cell cycle is highly conserved across human cell types
A network analysis of the combined data more efficiently identifies commonalities in cell cycle-related genes We identified 298 cell cycle genes up-regulated during G1/S-S and G2-M phase across independent studies in different human cell lines whereas direct comparison of the results of individual cell cycle studies showed only 96 common genes

Summary

Introduction

Cell division is central to the physiology and pathology of all eukaryotic organisms. A later study on primary human foreskin fibroblasts identified 480 cell cycle-associated genes [7] after synchronization of fibroblasts both with a doublethymidine block and by serum deprivation. The latter synchronisation method forces cells to enter a quiescent state (G0), from which they can re-enter proliferation as a cohort upon serum re-feeding [8]. The studies mentioned above isolated periodic signals from the gene expression profiles, apparent when multiple cell cycle events are monitored, in order to identify cell cycle-associated genes.

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