Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation
Creators
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1.
University of California, San Francisco
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2.
University of Valencia
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3.
California Institute of Technology
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.
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.Attached Files
Accepted Version - nihms932927.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.mp4
Supplemental Material - mmc3.mp4
Files
mmc1.pdf
Additional details
Identifiers
- PMCID
- PMC5802882
- Eprint ID
- 84649
- Resolver ID
- CaltechAUTHORS:20180202-090924087
Funding
- Deutsche Forschungsgemeinschaft (DFG)
- Generalitat Valenciana
- PROMETEOII/2014/075
- National Cancer Institute
- National Institute of Dental and Craniofacial Research (NIDCR)
- NIH
- DP5 OD012194
- NIH
- P50 GM081879
- Government of Chile
- NIH
- NS028478
- NIH
- HD032116
- John G. Bowes Research Fund
Dates
- Created
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2018-02-02Created from EPrint's datestamp field
- Updated
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2022-03-17Created from EPrint's last_modified field