When is a stem cell not really a stem cell?

August 26, 2007

Working with embryonic mouse brains, a team of Johns Hopkins scientists seems to have discovered an almost-too-easy way to distinguish between "true" neural stem cells and similar, but less potent versions. Their finding, reported this week in Nature, could simplify the isolation of stem cells not only from brain but also other body tissues.

What the researchers identified is a specific protein "signal" that appears to prevent neural stem cells - the sort that might be used to rebuild a damaged nervous system - from taking their first step toward becoming neurons. "Stem cells don't instantly convert into functional adult tissue," says author Nicholas Gaiano, Ph.D., assistant professor at the Institute for Cell Engineering. "They undergo a stepwise maturation where they gradually shed their stem cell properties."

The first step turns stem cells into "progenitor" cells by dictating how signals downstream of a protein called Notch, which regulates stem cells in many different tissues, are transmitted. One well known target of Notch is a protein called CBF1. To help study Notch signaling further, Gaiano and his team created genetically engineered mouse embryos that glow green when CBF1 is turned on.

To their surprise, they noticed that during brain development some of the brain cells generally thought to be neural stem cells stopped glowing, indicating that the CBF1 protein was no longer active in them. A closer look revealed that those cells that went dark were in fact no longer true neural stem cells, which can form all major brain cell types, but instead had aged into progenitor cells, which form mostly neurons.

They tested whether CBF1 was the critical switch by chemically knocking out the protein in neural stem cells. The knockout got the stem cells to rapidly convert to progenitor cells. "However, if we activated the CBF1 protein in progenitor cells we couldn't get them to shift back into stem cells," says Gaiano. "So whatever happens biochemically once CBF1 is turned off seems to create a one-way street."

Another recent study, using the mouse line generated by the Gaiano group, found that CBF1 signaling may play the same role in blood stem cells, leading Gaiano to suspect that his team's discovery might be a general "switch" distinguishing stem cells from progenitors in many different tissues.
-end-
The research was funded by the National Institutes of Health (NINDS), the Burroughs Wellcome Fund, and the Sidney Kimmel Foundation for Cancer Research.

Authors on the paper are Ken-ichi Mizutani, Keejung Yoon, Louis Dang, Akinori Tokunaga and Gaiano, all of Johns Hopkins.

On the Web:
http://www.hopkins-ice.org/neuro/int/gaiano.html
www.nature.com

Johns Hopkins Medicine

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.