The fountain of cellular youth
No one knows exactly how stem cells maintain their flexibility, and unfortunately, the mystery surrounding “stemness” hampers efforts to develop lifesaving therapies for conditions such as neurodegenerative disease, including Parkinson’s and Alzheimer’s. One City of Hope investigator is doing her best to dispel the mystery, though, by identifying the factors behind neural stem cells’ eternal youth.
photo: PAULA MYERSYanhong Shi
Yanhong Shi, Ph.D., assistant professor in the Division of Neurosciences, recently reported in Proceedings of the National Academy of Science how a protein called TLX maintains a critical component of stemness: neural stem cells’ ability to divide and reproduce themselves over and over, or “self-renew.” Until recently, scientists thought that once an adult lost nerve cells in the brain or spinal cord — whether through trauma, disease or aging — the cells were irreplaceable. That assumption has now been disproved. Scientists have found neural stem cells in adult mammalian brains. “These cells have the ability to self-renew and differentiate into brain cells like neurons,” Shi said.
Earlier in her career, Shi discovered that lab mice engineered to lack the TLX protein have far fewer neural stem cells in the adult brain than other mice. That finding implies that neural stem cells need the protein to renew themselves.
Her newest study reported that to keep neural stem cells youthful, TLX actually partners up with another protein called a histone deacetylase (HDAC).
Shi and City of Hope postdoctoral fellow Guoqiang Sun, Ph.D., showed that TLX and HDAC act as a team to slam the brakes on two genes that encourage neural stem cells to mature into adult nerve cells. Interestingly, one of those two genes does double duty. It not only pushes stem cell maturation, but also protects cells against cancer.
That could mean that the duo of TLX and HDAC controls not only the renewal of healthy stem cells that regenerate tissues, but also the activity of a more sinister type of cell that gives rise to a tumor, known as a “cancer stem cell.”
“This is a very important finding about mechanisms of how neural stem cells maintain stemness,” said Sun. “It could lead to potential drug discoveries — in one direction, for tissue-replacement therapies for diseases like Alzheimer’s or Parkinson’s, or in another, to target cancer stem cells.”
The research not only may lead to targets for therapies, but may also help scientists grow and acquire more adult neural stem cells for their studies.
Sun is the recipient of the Herbert Horvitz Postdoctoral Fellowship for Neuroscience Research. The National Institute of Neurological Disorders and Stroke also supported the study.