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STEMBAR SIGNED

Mechanisms and functional significance of diffusion barriers for asymmetric segregation of age in neural stem cells

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Project "STEMBAR" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT ZURICH 

Organization address
address: RAMISTRASSE 71
city: Zürich
postcode: 8006
website: http://www.unizh.ch

contact info
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name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT ZURICH CH (Zürich) coordinator 2˙000˙000.00

Map

 Project objective

Neural stem/progenitor cells (NSPCs) continue to generate new neurons throughout life in distinct regions of the mammalian brain. Adult neurogenesis has been implicated in brain function and altered neurogenesis has been associated with a number of neuropsychiatric diseases such as depression and cognitive ageing. A key feature of somatic stem cell division is the ability to divide asymmetrically and symmetrically for neurogenic and self-renewing cell division, respectively. However, it remains unknown how age is segregated in the context of somatic stem cell division, i.e., if the cellular history and the replicative age of the mother stem cell is passed onto its progeny. Thus, we hypothesized that – similar to the previously described barrier that exists in budding yeast – somatic stem cells, and more specifically NSPCs, form a diffusion barrier during cell division to retain aging or senescence factors within the stem cell, generating a mechanism for how age is asymmetrically distributed. Indeed, we found the existence of a diffusion barrier that is established during NSPC division, identifying a new mechanism of cellular segregation and asymmetry. With the program proposed here I aim i) to study the effects of the barrier on asymmetric segregation of aging factors and to develop novel tools to visualize the mammalian diffusion barrier, ii) to characterize the presence of a diffusion barrier in endogenous NSPCs in relation to cell division history, iii) to analyse the mechanisms underlying age-associated weakening of the NSPC diffusion barrier, and iv) to evaluate if genetic and pharmacological rescue of the barrier is sufficient to ameliorate the age-dependent decline of neurogenesis. The insights gained from the studies proposed here have the potential to substantially advance our understanding of NSPC biology, to identify a new mechanism underlying the neurogenic process, and to reshape our understanding of asymmetric cell division of somatic stem cells.

 Publications

year authors and title journal last update
List of publications.
2018 Gregor-Alexander Pilz, Sara Bottes, Marion Betizeau, David J. Jörg, Stefano Carta, Benjamin D. Simons, Fritjof Helmchen, Sebastian Jessberger
Live imaging of neurogenesis in the adult mouse hippocampus
published pages: 658-662, ISSN: 0036-8075, DOI: 10.1126/science.aao5056
Science 359/6376 2019-04-16
2018 Gerd Kempermann, Fred H. Gage, Ludwig Aigner, Hongjun Song, Maurice A. Curtis, Sandrine Thuret, H. Georg Kuhn, Sebastian Jessberger, Paul W. Frankland, Heather A. Cameron, Elizabeth Gould, Rene Hen, D. Nora Abrous, Nicolas Toni, Alejandro F. Schinder, Xinyu Zhao, Paul J. Lucassen, Jonas Frisén
Human Adult Neurogenesis: Evidence and Remaining Questions
published pages: 25-30, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.04.004
Cell Stem Cell 23/1 2019-04-16
2017 Marlen Knobloch, Gregor-Alexander Pilz, Bart Ghesquière, Werner J. Kovacs, Thomas Wegleiter, Darcie L. Moore, Martina Hruzova, Nicola Zamboni, Peter Carmeliet, Sebastian Jessberger
A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity
published pages: 2144-2155, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.08.029
Cell Reports 20/9 2019-04-16
2017 Darcie L. Moore, Sebastian Jessberger
Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells
published pages: 82-92, ISSN: 0962-8924, DOI: 10.1016/j.tcb.2016.09.007
Trends in Cell Biology 27/1 2019-04-16
2015 D. L. Moore, G. A. Pilz, M. J. Arauzo-Bravo, Y. Barral, S. Jessberger
A mechanism for the segregation of age in mammalian neural stem cells
published pages: 1334-1338, ISSN: 0036-8075, DOI: 10.1126/science.aac9868
Science 349/6254 2019-04-16

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