Arturo Alvarez-Buylla, PhD
	Adult Neural Stem Cells; Role in Neuronal Replacement and Cancer
	Email: abuylla@stemcell.ucsf.edu
Selected Publications Complete Publications

We are interested in the mechanisms of production of different types of adult brain cells including neurons and the possible connection between these progenitors and brain cancer.

Adult Neurogenesis. We have identified the stem cell and transit amplifying cells that serve as progenitors of new nerve and glial cells in the two main germinal regions of the adult brain: the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. Surprisingly, the primary progenitors correspond to astrocytes; cell previously considered differentiated glial cells. We have recently shown that adult astrocytes that function as neural stem cells are derived from neonatal radial glial, revealing the lineage of neural stem cells through postnatal brain development. In the SVZ, these progenitors give rise to cells that migrate to the olfactory bulb where they differentiate into multiple types of interneurons. One key question we are currently addressing is the origin of this diversity in neuronal types produced postnatally. We are also interested in the cellular interactions and molecules that constitute the adult germinal niche and the mechanisms of migration used by young neurons to navigate long distances through the adult brain.

Cell Fusion. Several laboratories recently proposed that hematopoeitic stem cells could become new neurons (transdifferentiate). We tested this hypothesis and found no evidence for transdifferentiation. Instead, we observed that nuclei from blood cells could end up inside some nerve cells. We are studying the mechanism of cell fusion between cells derived from blood and neurons, and its possible functional implications.

Cell Therapy. Adult neuronal production, migration and integration benefit specific regions of the adult mammalian brain. This is a serious limitation when considering the use of endogenous progenitors for brain repair. We have identified a subpopulation of embryonic progenitor cells that can migrate and integrate widely in the adult nervous system. In collaboration with 3 other laboratories at UCSF (Arnold Kriegstein, Scott Baraban and John Rubenstein), we are studying these progenitors to develop new strategies for brain repair.

Cancer. Recent observations indicate that SVZ astrocytes give rise to tumor-like growths when exposed to growth factors commonly implicated in brain cancer. This hints to a possible link between brain progenitor cells and cancer.

Work in the laboratory is helping understand how new neurons can be recruited into adult brain circuits and identifies possible culprits in brain cancer initiation.

Selected Publications

Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J.M., Fike, J.R., Lee, H.O., Pfeffer, K., Lois, C., Morrison, S.J. and Alvarez-Buylla, A. (2003) Fusion of bone marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968-73.

Sawamoto, K., Wichterle, H., Gonzalez-Perez, O., Cholfin, J., Yamada, M., Spassky, N., Murcia, N., Garcia-Verdugo, J.M., Marin, O., Rubenstein, J., Tessier-Lavigne, M., Okano, H. and Alvarez-Buylla, A. (2006) New Neurons Follow the Flow of Cerebrospinal Fluid in the Adult Brain. Science 311(5761):629-32.

Jackson, E.L., Garcia-Verdugo, J.M., Gil-Perotin, S., Roy, M., Quinones-Hinojosa, A., Vandenberg, S. and Alvarez-Buylla A. (2006) PDGFRalpha-Positive B Cells Are Neural Stem Cells in the Adult SVZ that Form Glioma-like Growths in Response to Increased PDGF Signaling. Neuron 51(2):187-99.

Information last updated April 2007