Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes

• Published in: Nature (London) Vol. 464; no. 7289; pp. 721 - 727
• Main Authors: Ellenberg, Jan, Neumann, Beate, Walter, Thomas, Hériché, Jean-Karim, Bulkescher, Jutta, Erfle, Holger, Conrad, Christian, Rogers, Phill, Poser, Ina, Held, Michael, Liebel, Urban, Cetin, Cihan, Sieckmann, Frank, Pau, Gregoire, Kabbe, Rolf, Wünsche, Annelie, Satagopam, Venkata, Schmitz, Michael H. A, Chapuis, Catherine, Gerlich, Daniel W, Schneider, Reinhard, Eils, Roland, Huber, Wolfgang, Peters, Jan-Michael, Hyman, Anthony A, Durbin, Richard, Pepperkok, Rainer
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2010; Nature Publishing Group
• Subjects: 631/1647/245/2186; 631/208/205; 631/80/641; Animals; Apoptosis; Biological and medical sciences; Cell cycle, cell proliferation; Cell division; Cell Division - genetics; Cell Movement - genetics; Cell physiology; Cell Survival - genetics; Cellular Biology; Chromosomes; Color; Fundamental and applied biological sciences. Psychology; Gene Knockdown Techniques; Genes; Genes - genetics; Genetics; Genome, Human - genetics; Genomics; Genotype & phenotype; HeLa Cells; Human genome; Humanities and Social Sciences; Humans; Kinetics; Life Sciences; Mice; Microscope and microscopy; Microscopy; Microscopy, Fluorescence - methods; Mitosis - genetics; Molecular and cellular biology; multidisciplinary; Phenotype; Proteins; Quality control; Reproducibility of Results; RNA Interference; Science; Science (multidisciplinary); Spindle Apparatus - genetics; Spindle Apparatus - metabolism; Subcellular Processes; Time Factors; Germany; Human; Phenotype; Gene; Microscopy; Cell division; Time; Genome
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature08869

Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the ∼21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community. Cell division genes revealed Jan Ellenberg and colleagues have used RNA interference to silence each of the approximately 21,000 protein-coding genes in a human cell line, then used high-throughput time-lapse imaging of live dividing cells to record the results. Phenotypes were scored quantitatively by computational image processing of at least six two-day movies per gene. Hundreds of genes were found to function in mitosis and other cellular processes including cell survival and migration. The entire data set is available as a public functional genomics resource at www.mitocheck.org. In the new News & View Forum, Jason Swedlow, Cecilia Cotta-Ramusino and Stephen Elledge consider the contribution of this remarkable data set to cell biology, and the challenge of drawing meaningful conclusions from future genome-wide screens. High-throughput microscopy combined with gene silencing by RNA interference is a powerful method for studying gene function. Here, a genome-wide method is presented for phenotypic screening of each of the ∼21,000 human protein-coding genes, using two-day imaging of dividing cells with fluorescently labelled chromosomes. The method enabled the identification of hundreds of genes involved in biological functions such as cell division, migration and survival.