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

被引:131
作者
Bar-Joseph, Ziv [1 ,2 ]
Siegfried, Zahava [3 ]
Brandeis, Michael [4 ]
Brors, Benedikt [5 ]
Lu, Yong [1 ]
Eils, Roland [5 ,6 ]
Dynlacht, Brian D. [7 ]
Simon, Itamar [3 ,8 ]
机构
[1] Carnegie Mellon Univ, Sch Comp Sci, Dept Comp Sci, Pittsburgh, PA 15213 USA
[2] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA
[3] Hebrew Univ Jerusalem, Sch Med, Dept Mol Biol, IL-91120 Jerusalem, Israel
[4] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel
[5] German Canc Res Ctr, Dept Theoret Bioinformat, D-69120 Heidelberg, Germany
[6] Heidelberg Univ, Inst Pharm & Mol Biotechnol, Dept Bioinformat & Funct Genom, D-69115 Heidelberg, Germany
[7] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
[8] NYU, Sch Med, Newyork Univ Canc Inst, New York, NY 10016 USA
关键词
deconvolution; expression profile;
D O I
10.1073/pnas.0704723105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:955 / 960
页数:6
相关论文
共 42 条
[1]   Genomic-scale gene expression profiling of normal and malignant immune cells [J].
Alizadeh, AA ;
Staudt, LM .
CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (02) :219-225
[2]   Deconvolving cell cycle expression data with complementary information [J].
Bar-Joseph, Ziv ;
Farkash, Shlomit ;
Gifford, David K. ;
Simon, Itamar ;
Rosenfeld, Roni .
BIOINFORMATICS, 2004, 20 :23-30
[3]   The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9 [J].
Borrow, J ;
Shearman, AM ;
Stanton, VP ;
Becher, R ;
Collins, T ;
Williams, AJ ;
Dube, I ;
Katz, F ;
Kwong, YL ;
Morris, C ;
Ohyashiki, K ;
Toyama, K ;
Rowley, J ;
Housman, DE .
NATURE GENETICS, 1996, 12 (02) :159-167
[4]   A common set of gene regulatory networks links metabolism and growth inhibition [J].
Cam, H ;
Balciunaite, E ;
Blais, A ;
Spektor, A ;
Scarpulla, RC ;
Young, R ;
Kluger, Y ;
Dynlacht, BD .
MOLECULAR CELL, 2004, 16 (03) :399-411
[5]   Repression of new p53 targets revealed by ChIP on chip experiments [J].
Ceribelli, Michele ;
Alcalay, Myriam ;
Vigano, Maria Alessandra ;
Mantovani, Roberto .
CELL CYCLE, 2006, 5 (10) :1102-1110
[6]   A genome-wide transcriptional analysis of the mitotic cell cycle [J].
Cho, RJ ;
Campbell, MJ ;
Winzeler, EA ;
Steinmetz, L ;
Conway, A ;
Wodicka, L ;
Wolfsberg, TG ;
Gabrielian, AE ;
Landsman, D ;
Lockhart, DJ ;
Davis, RW .
MOLECULAR CELL, 1998, 2 (01) :65-73
[7]   Transcriptional regulation and function during the human cell cycle [J].
Cho, RJ ;
Huang, MX ;
Campbell, MJ ;
Dong, HL ;
Steinmetz, L ;
Sapinoso, L ;
Hampton, G ;
Elledge, SJ ;
Davis, RW ;
Lockhart, DJ .
NATURE GENETICS, 2001, 27 (01) :48-54
[8]   Tumour biology -: Senescence in premalignant tumours [J].
Collado, M ;
Gil, J ;
Efeyan, A ;
Guerra, C ;
Schuhmacher, AJ ;
Barradas, M ;
Benguría, A ;
Zaballos, A ;
Flores, JM ;
Barbacid, M ;
Beach, D ;
Serrano, M .
NATURE, 2005, 436 (7051) :642-642
[9]  
Cooper Stephen, 2003, Cell Chromosome, V2, P1, DOI 10.1186/1475-9268-2-1
[10]   Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A [J].
Detwiller, KY ;
Fernando, NT ;
Segal, NH ;
Ryeom, SW ;
D'Amore, PA ;
Yoon, SS .
CANCER RESEARCH, 2005, 65 (13) :5881-5889