Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population.

Autor:	Harris L; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK., Rigo P; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK., Stiehl T; Institute of Applied Mathematics, Heidelberg University, 69120 Heidelberg, Germany; Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany; Bioquant Center, Heidelberg University, 69120 Heidelberg, Germany., Gaber ZB; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK., Austin SHL; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK., Masdeu MDM; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK., Edwards A; Advanced Sequencing Facility, The Francis Crick Institute, London NW1 1AT, UK., Urbán N; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK., Marciniak-Czochra A; Institute of Applied Mathematics, Heidelberg University, 69120 Heidelberg, Germany; Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany; Bioquant Center, Heidelberg University, 69120 Heidelberg, Germany., Guillemot F; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK. Electronic address: francois.guillemot@crick.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2021 May 06; Vol. 28 (5), pp. 863-876.e6. Date of Electronic Publication: 2021 Feb 12.
DOI:	10.1016/j.stem.2021.01.003
Abstrakt:	Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilize during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this stabilization of stem cell numbers in young adults is the result of coordinated changes in stem cell behavior. Although proliferating neural stem cells in juveniles differentiate rapidly, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomics, modeling, and label retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These changes in stem cell behavior result from a progressive reduction in expression of the pro-activation protein ASCL1 because of increased post-translational degradation. These cellular mechanisms help reconcile current contradictory models of hippocampal neural stem cell (NSC) dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species, including humans. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu