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Defining in vivo heterogeneity of adult neural stem cells at the single cell level

Research Project
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01.07.2014
 - 30.06.2019

Adult neural stem cells continuously generate neurons in restricted parts of the brain that functionally integrate into neural circuits. These endogenous stem cells may represent an important source of cells that can be stimulated for brain repair. The in vivo stem cells exhibit many features of astrocytes, glial cells classically associated with support functions. The ventricular-subventricular zone (V-SVZ) is the largest germinal region in the adult brain and generates different subtypes of olfactory bulb neurons, as well as oligodendrocytes and astrocytes. Recent work has suggested that adult neural stem cells exhibit regional heterogeneity in terms of their progeny. However little is known about the molecular programs and diversity of neural stem cells in vivo, due to a lack of markers to isolate them. We have recently defined a combination of markers that allows the prospective purification of quiescent and activated adult neural stem cells directly from the in vivo niche. We will couple this novel purification strategy with microfluidics-based single cell transcriptional profiling to illuminate the heterogeneity of adult neural stem cells. We propose to: 1) define the heterogeneity of adult neural stem cells by performing single cell transcriptional profiling of prospectively purified quiescent and activated adult neural stem cells isolated from different regions of the V-SVZ, 2) define the in vivo distribution and functional properties of the novel adult neural stem cell subpopulations. Together these studies will yield key insight into the heterogeneity and molecular programs of adult neural stem cells.

Publications

Chaker, Zayna, Codega, Paolo and Doetsch, Fiona (2016) ‘A mosaic world: puzzles revealed by adult neural stem cell heterogeneity’, WIREs Developmental Biology, pp. 640–658. Available at: https://doi.org/10.1002/wdev.248.

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Fiona Doetsch

Principal Investigator