Protein Identified as Cause of Stem Cell Self-Renewal

As scientists and doctors turn to stem cells as the newest frontier in regenerative medicine, they are beginning to learn more about the cells' function and what signals they use to either remain as stem cells or transform into adult tissue cells. Researchers at the University of Michigan have recently made a key finding in stem cell self-renewal that could have a large impact on both cancer medicine and tissue regeneration.

Through their study of stem cells, researchers were able to identify a key protein that seems to be the determining factor in whether stem cells continue to divide and proliferate as stem cells or begin transforming into the cells that make up adult tissue. The protein, called Klf4, maintains the character of the stem cells and promotes the continued division and replication until it is inactivated by two specific enzymes, ERK1 and ERK2. When the enzymes are signaled into action, they attach a small molecule of phosphate to Klf4, marking it for destruction by the cellular material. If the two enzymes are suppressed, the integrity of the Klf4 protein remains intact, and stem cells continue to divide and replicate as stem cells.

The researchers believe that learning more about the mechanisms of Klf4, ERK1, and ERK2 could have implications for both cancer research and regenerative medicine. Cancer cells tend to act similarly to stem cells, dividing and reproducing themselves unceasingly and leading to tumor growth. The function of Klf4 in cancer is controversial, but several studies have already pointed to it as a key factor in cancer cell growth. If scientists were able to inactivate Klf4 through the use of the two enzymes, they may be able to slow the aggressive growth of cancer cells.

For regenerative medicine, the focus remains on allowing stem cells to continue to grow and reproduce until a sufficient number of cells has been formed for tissue regeneration. If scientists were able to keep the Klf4 protein active in stem cells, they may be able to create drugs that make the repair and regeneration of healthy tissue possible following damage from heart disease, diabetes, aging, and more.

The results of the study have been published in the journal Nature: Structure and Molecular Biology and point to an exciting new step in the path of stem cell research.


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