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Stem Cell Reports. 2017 Dec 12;9(6):1931-1947. doi: 10.1016/j.stemcr.2017.10.005. Epub 2017 Nov 9.

Non-monotonic Changes in Progenitor Cell Behavior and Gene Expression during Aging of the Adult V-SVZ Neural Stem Cell Niche.

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Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Neural Stem Cell Institute, Rensselaer, NY 12144, USA. Electronic address:
Electrical and Computer Engineering, Drexel University, Philadelphia, PA 19104, USA.
Neural Stem Cell Institute, Rensselaer, NY 12144, USA; Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208, USA.
Neural Stem Cell Institute, Rensselaer, NY 12144, USA. Electronic address:


Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18, and 22 months, we found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1+ progenitor cells decreased in number and proliferation between 2 and 18 months but increased between 18 and 22 months. Time-lapse lineage analysis of 944 V-SVZ cells showed that age-related declines in neurogenesis were recapitulated in vitro in clones. However, activated type B/type C cell clones divide slower at 2 to 18 months, then unexpectedly faster at 22 months, with impaired transition to type A neuroblasts. Our findings indicate that aging of the V-SVZ involves significant non-monotonic changes that are programmed within progenitor cells and are observable independent of the aging niche.


aging; lineage analysis; neural stem cells; subventricular zone

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