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Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation

Obernier, Kirsten and Cebrian-Silla, Arantxa and Thomson, Matthew and Parraguez, José Ignacio and Anderson, Rio and Guinto, Cristina and Rodriguez, José Rodas and Garcia-Verdugo, José-Manuel and Alvarez-Buylla, Arturo (2018) Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation. Cell Stem Cell, 22 (2). pp. 221-234. ISSN 1934-5909. PMCID PMC5802882. https://resolver.caltech.edu/CaltechAUTHORS:20180202-090924087

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.stem.2018.01.003DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802882PubMed CentralArticle
ORCID:
AuthorORCID
Garcia-Verdugo, José-Manuel0000-0001-9872-6499
Alvarez-Buylla, Arturo0000-0003-4426-8925
Additional Information:© 2018 Elsevier Inc. Received 17 January 2017, Revised 16 October 2017, Accepted 2 January 2018, Available online 1 February 2018. Author Contributions: Conceptualization, K.O. and A.A.-B; Methodology, K.O., A.C.-S., and M.T.; Formal Analysis, K.O., A.C.-S., and M.T.; Investigation, K.O., A.C.-S., J.I.P., R.A., C.G., and J.R.R; Software, M.T.; Resources, J.-M.G.-V. and A.A.-B.; Writing – Original Draft, K.O., A.C.-S., M.T., and A.A.-B.; Visualization, K.O., A.C.-S., and M.T.; Supervision, J.-M.G.-V. and A.A.-B.; Funding Acquisition, K.O. and A.A.-B. Declaration of Interests: A.A.-B. is co-founder and on the Scientific Advisory Board of Neurona Therapeutics. We would like to thank Daniel Lim, Luis Fuentealba, and members of the Alvarez-Buylla lab for helpful discussions. K.O. was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation). A.C.-S. and J.-M.G.-V. were supported by Generalitat Valenciana (PROMETEOII/2014/075). M.T. received support from the NIH Office of the Director (OD), the National Cancer Institute, and the National Institute of Dental and Craniofacial Research (NIDCR)NIH DP5 OD012194, as well as the UCSF Center for Systems and Synthetic Biology (NIGMS) P50 GM081879. J.I.P. was supported by the Chilean government (Becas Chile). Work in the Alvarez-Buylla laboratory was supported by NIH grants NS028478 and HD032116 and a generous gift from the John G. Bowes Research Fund. A.A.-B. is the Heather and Melanie Muss Endowed Chair and Professor of Neurological Surgery at UCSF.
Funders:
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Generalitat ValencianaPROMETEOII/2014/075
National Cancer InstituteUNSPECIFIED
National Institute of Dental and Craniofacial Research (NIDCR)UNSPECIFIED
NIHDP5 OD012194
NIHP50 GM081879
Government of ChileUNSPECIFIED
NIHNS028478
NIHHD032116
John G. Bowes Research FundUNSPECIFIED
Subject Keywords:neural stem cells; B1 cells; ventricular-subventricular zone; self-renewal; neurogenesis; symmetric division; division mode; lineage tracing; time-lapse imaging; aging
Issue or Number:2
PubMed Central ID:PMC5802882
Record Number:CaltechAUTHORS:20180202-090924087
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180202-090924087
Official Citation:Kirsten Obernier, Arantxa Cebrian-Silla, Matthew Thomson, José Ignacio Parraguez, Rio Anderson, Cristina Guinto, José Rodas Rodriguez, José-Manuel Garcia-Verdugo, Arturo Alvarez-Buylla, Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation, Cell Stem Cell, Volume 22, Issue 2, 1 February 2018, Pages 221-234.e8, ISSN 1934-5909, https://doi.org/10.1016/j.stem.2018.01.003. (https://www.sciencedirect.com/science/article/pii/S1934590918300031)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84649
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:02 Feb 2018 17:33
Last Modified:15 Apr 2020 18:13

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