Researchers at the School of Medicine have identified a new protein critical to the production of induced pluripotent stem cells, or iPS cells.

The protein, NKX3-1, has previously been shown to play a role in prostate development and tumor suppression. It can substitute for one of the four proteins first identified in 2007 by stem cell researcher Shinya Yamanaka, MD, PhD, as sufficient to prod mature cells like those in the skin or blood to become iPS cells—a transformation known in the stem cell world as reprogramming.

The discovery creates a peephole into the black box of cellular reprogramming and may lead to new ways to generate iPS cells in the laboratory. It was made possible by the use of a unique laboratory model for reprogramming that tightly synchronizes the earliest steps of the process. “This is a crucial regulator that would not have been discovered any other way,” said Helen Blau, PhD, professor of microbiology and immunology. “It appears within 2 hours of the initiation of reprogramming, and then it’s gone. But it’s absolutely critical. If we eliminate it, reprogramming doesn’t happen.”

Blau, the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Foundation Laboratory for Stem Cell Biology, is the senior author of the research, which was published online July 16 in Nature Cell Biology. Postdoctoral scholar Thach Mai, PhD, is the lead author.

The ability to reprogram mature cell types, such as skin cells, into pluripotent stem cells by the addition of just four proteins, called Yamanaka factors, captivated the scientific world and led to a Nobel Prize in 2012 for Yamanaka. Since then, countless researchers worldwide have used the technique to create iPS cells for study or potential clinical use.