Researchers say they have discovered the gene that regulates stem cell ability to self-renew and to differentiate into highly specialized types. This means they could program stem cells to become certain cells or do repair automatically.
“You could call this a ‘theory-of-everything’ for stem cells,” said senior author Dr. Michael Rudnicki, Senior Scientist and Professor at the Ottawa Health Research Institute and the University of Ottawa, referring to the often-cited theory of everything for physics.
For more than 25 years, stem cells have been defined based on what they can become: more of themselves, as well as multiple different specialized cell types. But as genetic techniques have become increasingly powerful, many scientists have sought a more molecular definition of stem cells, based on the genes they express.
Manual curation of databases reveals highly enriched Gene Ontology (GO) categories for Oct4 positively (A) and negatively (B) correlated genes. Numbers displayed represent percentage of unique transcripts attributed to each category with only the most abundant categories listed individually.doi:10.1371/journal.pone.0000553.g002
A team of Canadian scientists has identified 1,155 genes under the control of a gene called Oct4 considered to be the master regulator of the stem cell state. A comprehensive molecular definition of stem cells is emerging: according to this research, stem cells are cells that keep their DNA packaged in a flexible format, keep cell division tightly controlled, prevent signals that might trigger death, repair DNA very effectively, and reinforce all of these characteristics by tightly controlling how molecules can move within the nucleus.
While previous studies have tried to compare gene expression in different types of stem cells, the strategy used in this study was unique. Rather than simply searching for any genes expressed by stem cells, the researchers looked for genes whose expression was also correlated with the master stem cell regulator gene Oct4. They also applied very rigorous analysis methods, using data from StemBase, the largest stem cell gene expression database in the world.
Designed by bioinformaticist Dr. Miguel Andrade, the database includes data from thousands of DNA microarrays submitted mainly by scientists in Canada’s Stem Cell Network. All data is freely available at www.stembase.com.
Lead author Ms. Pearl Campbell noted that understanding how stem cells maintain their identity is key to the emerging field of regenerative medicine. “These findings may help us to understand how the key genes which control cell fate are regulated, and how, when dysregulated, they can lead to disease. This may ultimately allow us to develop targeted therapies to stimulate adult stem cells within our own bodies to repair damaged tissues, and may provide further areas of exploration for the treatment of cancer.”
Oct4 Targets Regulatory Nodes to Modulate Stem Cell Function, Campbell PA, Perez-Iratxeta C, Andrade-Navarro MA, Rudnicki MA