Similar to great oaks growing from tiny acorns, the millions of different cells in the human body essentially spring from one embryonic stem cell. As it divides and replicates, it forms either a clone of itself, or a differentiated cell that travels a more specific path – as a skin cell, heart cell, blood cell, brain cell or myriad other specific cells with limited roles and life.
This potential to become any cell is both the promise and peril of using stem cells to treat diseases such as cancer. To make stem cell therapies safe and effective, scientists need to be able to control how stem cells replicate and what type of cells they become.
City of Hope researchers Gerd Pfeifer, Ph.D., and Qiang Lu, Ph.D., have helped move the world one step closer to this goal by being the first to uncover the process of how neural stem cells differentiate into neurons and other specific cells of the central nervous system. Their findings are available online in advance of publication in the journal Cell Reports.
“This is the first time anyone has been able to understand and describe the brain development process on this level,” said Pfeifer, the Lester M. and Irene C. Finkelstein Chair in Biology and professor in the Department of Cancer Biology. To help understand the discovery, a little education in DNA is necessary. All DNA is made of four molecules – adenine, guanine, thymine and cytosine. The body grows, functions and develops by reading the blueprints laid out in the arrangement of these four molecules in the gene – a specific section of DNA – and carrying out these instructions.
During the reading and production process, cytosine is modified into different versions – notably 5-methylcytosine and 5-hydroxymethylcytosine. Lu and Pfeifer examined the activity of these two cytosine modifications during neurogenesis in the embryonic mouse brain and found their relationship to how neural stem cells differentiate into neurons and other specific cells of the central nervous system.
In a nutshell, 5-hydroxymethylcytosine plays a big role in neurogenesis, activating genes that lead to neuron production and development in the growing brain. Understanding how the brain develops opens the door to greater understanding of how neurological disorders may develop through defects or subtle shifts in the process.
“We will be conducting further studies for a more detailed understanding of the specific proteins involved in this process,” said Lu, associate professor in the Department of Neurosciences.