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Stem Cells, You Were Always On My Mind

Stem Cells, You Were Always On My Mind

Posted on December 23, 2014

Logo of the 2014 Society of Neuroscience meeting.
I recently had the opportunity to attend the 2014 Society for Neuroscience annual meeting held in Washington D.C. It was a fantastic meeting but, as anyone who has attended knows, the amount of information presented feels like a shotgun blast to the face. There were hundreds of presentations and posters with topics that varied from epigenetics in learning and memory to how a neuroscientist could use the Oculus Rift to test a subject’s responses to a frightening visual and auditory stimulus all while being in a controlled lab environment.One hot topic that was particularly exciting was the focus on adult neurogenesis. Not a new concept but one that has gained a lot of attention in the last decade or so. Emerging data shows several specialized regions in the brain which have active neurogenesis including, most recently, the adult striatum.

Due to the growing interest in adult stem cells scientists have been furiously working to classify stem cell populations in different tissues, as well as determine how they function. At the SFN meeting I was lucky to learn a little more about which cells in the brain function as stem cells and how our brains maintain this precious population. Dr. Fiona Doetsch from Columbia University was one of the presidential speakers who gave a talk entitled “Stem Cells in the Brain: Glial Identity and Niches.” This wonderful lecture highlighted her findings of a glial cell type that resides in the subventricular zone of adult mammalian brains. This is a self renewing cell type that gives rise to progeny that can be classified as different subtypes depending on what stage they are at while on the way to generating a new neuron.

Treatment of mice with ara-C eliminates migrating neuroblasts and precursor cells, essentially eliminating active neurogenesis, but within four days after this treatment you start to see new neurogenesis and only GFAP positive glial remain. Further characterization of these cells show they are GFAP+/BLBP+/GLAST+ astrocytes which become activated, and express EGFR+ & nestin+, by signaling from the surrounding microenvironment. Once these cells become transamplifying cells they lose their GFAP expression on their way to differentiating into neurons. The Doetsch Lab has also shown that these cell types inhabit a special “stem cell niche” that helps maintain the stem cell population. This niche is a unique microenvironment made up of specific cell types, extracellular matrix, and structure that all support the astrocytic stem cells. One example of a novel attribute within this niche is the presence of specialized vascular cells. These cells lack astrocyte endfeet, and pericyte, coverage and directly contact these glial stem cells to provide signals which can help the cells maintain quiescence. Continued research in the Doetsch Lab is focused on defining the signals that tell these stem cells when to proliferate, where to migrate, and how to connect to the existing network of neurons; one possibility being signaling by regional innervation into the niche. Lineage mapping of these neural stem cells and insight into how the brain regulates communication to these cells provides the groundwork so that we may elucidate the functional consequences of adult neurogenesis. Moreover, these findings will help guide understanding of brain repair and the development of CNS pathologies.

It is clear from this lecture that as scientists working on stem cells, we should all try and think of ways in which we can take advantage of these novel adult stem cell populations in our research, and how these cells might be affected during disease. Although these cells have been designated a very important role in the population one cannot ignore those others in the population which provide societal support and allow these individuals to properly function. All individuals and cell types that make up the larger regional population deserve our focus if we are to truly decipher how biological processes occur and diseases develop.

Ryan Lim, MA, CIRM fellow

Ryan Lim, MA, is a current CIRM predoctoral fellow working in the laboratory of Dr. Leslie Thompson at the Sue & Bill Gross Stem Cell Research Center at the University of California, Irvine (UCI). His current research is focused on using computational biology methods and patient-derived induced pluripotent stem cells to develop cell signatures that define Huntington’s disease. His past experience is in developing novel peptide decorated nanocarriers for targeting and treating breast cancer stem cell. This work was conducted in the laboratory of Dr. Kit Lam at the University of California, Davis (UCD) and lead to his interest in stem cell research.

 
Citations
1. Ernst, A. et al. Neurogenesis in the striatum of the adult human brain. Cell 156, 1072-1083, doi:10.1016/j.cell.2014.01.044 (2014).
2. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703-716 (1999).
3. Tavazoie, M. et al. A specialized vascular niche for adult neural stem cells. Cell stem cell 3, 279-288, doi:10.1016/j.stem.2008.07.025 (2008).
4. Delgado, A. C. et al. Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction. Neuron 83, 572-585, doi:10.1016/j.neuron.2014.06.015 (2014).