Stem Cells are Wired for Cooperation, Down to the DNA

Newswise We often think of human cells as tiny computers that perform assigned tasks, where disease is a result of a malfunction. But in the current issue of Science, researchers at The Mount Sinai Medical Center offer a radical view of health seeing it more as a cooperative state among cells, while they see disease as result of cells at war that fight with each other for domination.

Their unique approach is backed by experimental evidence. The researchers show a network of genes in cells, which includes the powerful tumor suppressor p53, which enforce a cooperative state within cellsrather like the queen bee in a beehive. Disease or disorder occurs when these enforcer genes are mutated, allowing competition between cells to ensue.

Both competition and cooperation drive evolution, and we are wired for cooperation all the way down to our genes, says the studys senior investigator, Thomas P. Zwaka, MD, PhD, Professor at the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai.

The findings, if backed by future research, offer a new way to address disease, Dr. Zwaka says. Understanding the genetic basis of cooperative and competitive cellular behaviors could explain how cancer and immune system dysfunction develops, he says. If a cell has lost a gene that fosters communication among cells, it may dominate other cells by ignoring signals to stop proliferating. It also makes sense that the immune system might detect and attack cells that are not cooperating. Failure to cooperate may also underlie development of birth defects.

He adds that it may be possible to flip the cooperation switch back on therapeutically, or to manipulate stem-like cells to misbehave in a way that produces replacement cells for regenerative medicine.

Cell misbehave, they are unpredictable. They do not operate like little machines, he says. What our study suggests is that cooperation is so central to our evolution that we have genetic mechanisms to protect us against cheating and dominating behavior.

A network of genes with an ancient function The research team, which also includes study first author Marion Dejosez, PhD, Assistant Professor at the Icahn School at Mount Sinai, took a long view toward the behavior of cells. They wondered how it was that cells, which lived on earth as single units for hundreds of millions of years, could effectively bundle themselves together to perform specific tasks. Cells started somehow to form alliances, and to cooperate, and obviously this multicellularity had certain advantages.

But they also questioned what happened to the cheating behavior that can be seen in single cells, such as amoeba, that live in colonies competitive behavior that allows the cell to gain a reproductive advantage without contributing its fair share to the community.

They conducted a genetic screen in stem cells to look for mutants that allow cells to misbehaveto become a little antisocial and do things they wouldnt normally do, Dr. Zwaka says. The screen picked up about 100 genes, which seem to cluster together into a network.

The team focused on three of those genesp53, long known as the guardian of the genome, Topoisomerase 1 (Top1), which control genomic stability, and olfactory receptors involved in the sensation of smell.

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Stem Cells are Wired for Cooperation, Down to the DNA