Less plasticity in adult stem cells

Adult neural stem cells in the mouse brain are less plastic than previously thought, according to a study published online this week in Science. The authors found that a stem cell's position in the brain determines the type of neuron it generates.

As a result, it may be more difficult to coax adult neural stem cells into becoming various types of neurons than some researchers have predicted, according to senior author Arturo Alvarez-Buylla of the University of California, San Francisco.

"The whole idea of flexibility among adult neural stem cells has to be, I think, reconsidered," Alvarez-Buylla told The Scientist. Instead, there appears to be a "mosaic of different types of primary progenitors giving rise to all of these different types of neurons," he said.

Neural stem cells in the subventricular zone (SVZ) of the mammalian brain generate neurons throughout the animal's life that migrate to the olfactory bulb and differentiate into several different cell types. Many researchers have believed that these stem cells are homogenous and multipotent until they mature in the olfactory bulb, Alvarez-Buylla said. "That was the model that many people, including ourselves, were working under."

Recent work, however, suggested that newly born neurons become distinct from one another before they reach the olfactory bulb. To see if the stem cells that generate these neurons in the SVZ are also diverse, researchers led by Florian T. Merkle, also of UCSF, labeled them with green fluorescent protein in different areas of the SVZ and followed their progeny. They found that each region of the SVZ gave rise to a specific subset of neurons in the olfactory bulb.

The researchers next dissected labeled stem cells out of one SVZ region and grafted them onto a different region in a donor mouse. They found that the stem cells' original positions still specified the fates of the mature neurons, showing that a factor intrinsic to the cells governs their fates.

Last, the researchers found that the cells retained memory of their regions of origin even when they were cultured with no environmental cues.

Merkle and his colleagues speculate that transcription factors could encode positional information in the stem cells and their progeny.

"The results are convincing," said Michael Sofroniew of the University of California, Los Angeles, who was not involved in the work. "In a sense, this is not surprising at all. It fits in with what people in development have been saying for some time," he said.

Studies have shown that the potential of neural progenitors during embryonic brain development is also determined by a spatial code.

"Probably the same rules apply in the adult brain as do in the embryonic brain," agreed Kenneth Campbell of Children's Hospital Research Foundation in Cincinnati, Ohio, also not a co-author. "There's been a kind of disconnect in the field of adult neurogenesis, with those notions that you could procure stem cells and then generate any type of neuron," he told The Scientist. "Their data suggest that that's maybe not the case and rather that a lot of these progenitor cells... have really specific programs that they're going to run as they start to differentiate."

The paper's findings predict difficulties in using adult stem cells to treat neurological disease, Campbell said. "I think now most people are starting to really realize that that's not something that's going to easily be done."

It remains possible, however, that scientists could manipulate adult neural stem cells in vitro to make them more flexible, Sonofriew said. "If you take these cells out of the brain and put them in tissue culture, you can make them do all sorts of things that they might not necessarily do in vivo."

Melissa Lee Phillips
mail@the-scientist.com

Links within this article

R. Lewis, "Stem cells... an emerging portrait," The Scientist, July 4, 2005.
http://www.the-scientist.com/article/display/15592/

F.T. Merkle et al., "Mosaic organization of neural stem cells in the adult brain," Science, published online July 5, 2007.
http://www.sciencemag.org


Arturo Alvarez-Buylla
http://www.ucsf.edu/neurosc/faculty/neuro_alvarez-buylla.html

T. Powledge, "Neurogenesis happens in humans, too," The Scientist, February 15, 2007.
http://www.the-scientist.com/news/display/52849/

F.H. Gage, "Mammalian neural stem cells," Science, February 25, 2000.
http://www.the-scientist.com/pubmed/10688783

M.A. Hack et al., "Neuronal fate determinants of adult olfactory bulb neurogenesis," Nature Neuroscience, July 2005.
http://www.the-scientist.com/pubmed/15951811

Florian T. Merkle
http://www.stemcell.medschool.ucsf.edu/Research/labs/alvarez-buylla/bios/merkle_florian.aspx

Michael Sofroniew
http://www.uclaaccess.ucla.edu/UCLAACCESS/Web/Faculty.aspx?ri=1256

K. Campbell, "Dorsal-ventral patterning in the mammalian telencephalon," Current Opinion in Neurobiology, February 2003.
http://www.the-scientist.com/pubmed/12593982

Kenneth Campbell
http://www.cincinnatichildrens.org/svc/find-professional/c/kenneth-campbell.htm

L. Defrancesco, "Stem cell researchers take on Parkinson's," The Scientist, May 28, 2001.
http://www.the-scientist.com/article/display/12413