4D imaging analysis of the aging mouse neural stem cell niche reveals a dramatic loss of progenitor cell dynamism regulated by the RHO-ROCK pathway
Open accessAbstract
In the adult ventricular-subventricular zone (V-SVZ), neural stem cells (NSCs) give rise to transit-amplifying progenitor (TAP) cells. These progenitors reside in different subniche locations, implying that cell movement must accompany lineage progression, but the dynamic behaviors of adult NSCs and TAPs remain largely unexplored. Here, we performed live time-lapse imaging with computer-based image analysis of young and aged 3D V-SVZ wholemounts from transgenic mice with fluorescently distinguished NSCs and TAP cells. Young V-SVZ progenitors are highly dynamic, with regular process outgrowth and retraction and cell migration. However, these activities dramatically declined with age. An examination of single-cell RNA sequencing (RNA-seq) data revealed age-associated changes in the Rho-Rock pathway that are important for cell motility. Applying a small molecule to inhibit ROCK transformed young into old V-SVZ progenitor cell dynamic behaviors. Hence RHO-ROCK signaling is critical for normal adult NSC and TAP movement and interactions, which are compromised with age, concomitant with the loss of regenerative ability.
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In the brain, old progenitors exhibit reduced differentiation dynamics during ageing, and their fate potential is predominantly skewed towards astrocytes.
“In the brain, old progenitors exhibit reduced differentiation dynamics during ageing45, and their fate potential is predominantly skewed towards astrocytes46.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [45]
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- Authors
- Zhao, X., Fisher, E. S., Wang, Y., Zuloaga, K., Manley, L., & Temple, S.
- Affiliations
- Neural Stem Cell Institute (US)
- Albany Medical Center Hospital (US)
- Corresponding author
- Temple, Sally
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 17
- Issue
- 2
- Pages
- 245-258
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC8828534
- OpenAlex
- W4206672934
- Cited by
- 10
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- NIH
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- neural stem cells, aging, ventricular-subventricular zone, Rho/ROCK signaling, cell motility, cell migration, neural stem cell niche, ROCK inhibition, regenerative capacity, adult neurogenesis
- MeSH terms
- Aging, Amides, Animals, Cell Movement, Mice, Transgenic, Pyridines, Signal Transduction, Lateral Ventricles, rho GTP-Binding Proteins, Mice, rho-Associated Kinases, Stem Cell Niche, Neural Stem Cells, Time-Lapse Imaging
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