The researchers identified a certain protein 'signal' that apparently prevents neural stem cells - the type that may be used to repair damage to the nervous system - from taking the first step towards becoming neurons (mature nerve cells)
In a study of embryonic mouse brains, a group of scientists at Johns Hopkins University discovered an apparently almost-too-easy-to-believe way to distinguish between true neuronal stem cells and similar cells with less developmental potential. Their findings, published in Nature magazine, can simplify the process of isolating stem cells not only from the brain but from other tissues.
What the researchers identified is a certain protein 'signal' that apparently prevents neural stem cells - the type that may be used to repair damage in the nervous system - from taking the first step towards becoming neurons (mature nerve cells). "Stem cells do not immediately become functional mature tissue cells," says the author of the article Dr. Nicholas Gaiano, assistant professor at the Cell Engineering Institute. "They undergo maturation in stages in which they gradually lose their characteristics as stem cells."
The first step turns the stem cells into 'progenitor' cells by determining how signals are transmitted that are controlled by a protein called Notch (downstream signals, downstream of notch), which regulates stem cells in many tissues. A known target of Notch is a protein called CBF1. In order to study Notch signaling in depth, Gaiano and his group created genetically engineered mouse embryos that glow green when CBF1 is activated.
To their surprise, they noticed that as the brain developed, some of the brain cells that were considered stem cells stopped glowing, meaning the CBF1 protein in them stopped being active. A deeper look revealed that those cells that stopped glowing are actually no longer true neural stem cells, which can create all types of brain cells, but actually 'grew' to be progenitor cells that create mainly neurons.
They tested whether CBF1 is the critical switch by chemically silencing it in neuronal stem cells. The silencing caused the stem cells to quickly turn into progenitor cells. "But, if we activated CBF1 in the progenitor cells, we couldn't get them to turn back into stem cells," Gaiano said. "So what happens chemically when CBF1 is turned off probably creates a one-way pathway."
More recently, using the mouse strain created by Gaiano's group, he found that CBF1 signaling plays a similar role in blood-producing stem cells, which leads Gaiano to suspect that his group has discovered a general switch that distinguishes stem cells from progenitors in many tissues.
The study was funded by the National Institutes of Health (NINDS), the Buros Wellcome Foundation, and the Sidney Kimmel Foundation for Cancer Research. The authors of the article are Ken-ichi Mitsutani, Qicheng Yun, Louis Dang, Akinori Tokenga and Gayano. All from Johns Hopkins.
