Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation

Publication date: 1 February 2018
Source:Cell Stem Cell, Volume 22, Issue 2
Author(s): Kirsten Obernier, Arantxa Cebrian-Silla, Matthew Thomson, José Ignacio Parraguez, Rio Anderson, Cristina Guinto, José Rodas Rodriguez, José-Manuel Garcia-Verdugo, Arturo Alvarez-Buylla
Somatic stem cells have been identified in multiple adult tissues. Whether self-renewal occurs symmetrically or asymmetrically is key to understanding long-term stem cell maintenance and generation of progeny for cell replacement. In the adult mouse brain, neural stem cells (NSCs) (B1 cells) are retained in the walls of the lateral ventricles (ventricular-subventricular zone [V-SVZ]). The mechanism of B1 cell retention into adulthood for lifelong neurogenesis is unknown. Using multiple clonal labeling techniques, we show that the vast majority of B1 cells divide symmetrically. Whereas 20%–30% symmetrically self-renew and can remain in the niche for several months before generating neurons, 70%–80% undergo consuming divisions generating progeny, resulting in the depletion of B1 cells over time. This cellular mechanism decouples self-renewal from the generation of progeny. Limited rounds of symmetric self-renewal and consuming symmetric differentiation divisions can explain the levels of neurogenesis observed throughout life.

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Teaser

Obernier et al. show that juvenile/adult neural stem cells (NSCs) generate progeny or self-renew through symmetric divisions. The prevailing consuming symmetric divisions progressively deplete NSCs, yet this mechanism enables lifelong generation of large numbers of neurons for the olfactory bulb while decoupling proliferation from differentiation.


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