As the brain develops, stem cells proliferate like crazy. These cells are like young medical students – they haven’t yet chosen a specialty. At some point, a very important switch is thrown and stem cells stop increasing in number and start differentiating into specialized brain cells with defined functions and abilities. Some will become neurons and carry messages that determine what we think or do, while others will become some other type of brain cell that supports or protects neurons. But no matter what they ultimately become, these stem cells have to stop multiplying at some point. Otherwise, too many accumulate and a brain tumor results.What tells stem cells to quit dividing and start differentiating?
Dr. Antonio Iavarone, professor at Columbia University, addressed that question at the June meeting of the Southern California Stem Cell Consortium. Dr. Iavarone was invited by Dr. Evan Snyder, professor at Sanford-Burnham.
In his introduction to Dr. Iavarone’s talk, Dr. Snyder explained that, in addition to fostering collaboration between labs and institutions, “The purpose of these SoCal Stem Cell Consortium meetings is education and data-sharing.”
And Dr. Iavarone had a lot of data to share. He described several ongoing stem cell projects in his lab, including a story about a protein in the brain known as “Id.”
Id might just be the master regulator of that switch that determines the difference between normal stem cell growth and out-of-control cell growth. He described how Id keeps stem cells as stem cells – increasing in number, but not settling down and choosing a specialty. When Dr. Iavarone and his colleagues turned Id off, stem cells were allowed to stop dividing and start differentiating.
Like almost everything else in the body, brain development is a careful balance. On one hand, Id is necessary to ensure proper brain development. On the other hand, if it isn’t turned off at the appropriate time, stem cell growth continues unchecked, the cells never specialize and a brain tumor forms. Indeed, Dr. Iavarone showed that Id is more prevalent in glioblastoma and neuroblastoma tumors, two of the more common types of brain cancer. Not only that, but he also found that the more Id a tumor has, the more aggressive it is – bad news for a patient’s prognosis.
So what if we can manipulate Id to restore the balance of stem cell growth in patients? A drug that inhibits Id might halt a growing tumor; a drug that activates Id might help repair or replace damaged neurons to treat neurodegenerative diseases like Parkinson’s or Alzheimer’s.
“We are now beginning to screen chemical libraries to find molecules that target Id,” Dr. Iavarone explained. “We believe anti-Id agents will be effective at inhibiting tumor growth.”