Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche
Open accessAbstract
Adult neurogenic niches harbor quiescent neural stem cells; however, their in vivo identity has been elusive. Here, we prospectively isolate GFAP(+)CD133(+) (quiescent neural stem cells [qNSCs]) and GFAP(+)CD133(+)EGFR(+) (activated neural stem cells [aNSCs]) from the adult ventricular-subventricular zone. aNSCs are rapidly cycling, highly neurogenic in vivo, and enriched in colony-forming cells in vitro. In contrast, qNSCs are largely dormant in vivo, generate olfactory bulb interneurons with slower kinetics, and only rarely form colonies in vitro. Moreover, qNSCs are Nestin negative, a marker widely used for neural stem cells. Upon activation, qNSCs upregulate Nestin and EGFR and become highly proliferative. Notably, qNSCs and aNSCs can interconvert in vitro. Transcriptome analysis reveals that qNSCs share features with quiescent stem cells from other organs. Finally, small-molecule screening identified the GPCR ligands, S1P and PGD2, as factors that actively maintain the quiescent state of qNSCs.
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G-protein coupled receptor (GPCR) signaling associated with NSC quiescence was enriched in the male septal wall.
“In contrast, G-protein coupled receptor (GPCR) signaling associated with NSC quiescence (Codega et al., 2014) was enriched in the male septal wall (Figure 2C; Table S3).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Codega et al., 2014
All profiling studies in the adult V-SVZ, including recent low-throughput single-cell studies, have focused only on the lateral wall and the neuronal lineage.
“Although transcriptome analysis in the postnatal V-SVZ has uncovered molecular differences between the dorsal and the lateral walls (Azim et al., 2015), all profiling studies in the adult V-SVZ, including recent low-throughput, single-cell studies, have focused only on the lateral wall and the neuronal lineage (Basak et al., 2018; Codega et al., 2014; Dulken et al., 2017; Llorens-Bobadilla et al.,”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Codega et al., 2014
The findings underline the sensitivity and power of single-cell transcriptomics to reveal differences in cell identities and changes within individual cell types under different treatments and conditions, including organismal aging.
“Our findings, in agreement with recent studies, underline the sensitivity and power of single-cell transcriptomics not only to reveal differences in cell identities, but also to reveal changes within individual cell types under different treatments and conditions 23,26,27,70 , including organismal aging 59,60 .”
From Single-cell transcriptomic profiling of the aging mouse brain (2019) · cites this paper as [60]
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- Authors
- Codega, P., Silva-Vargas, V., Paul, A., Maldonado-Soto, A. R., DeLeo, A. M., Pastrana, E., & Doetsch, F.
- Affiliations
- Columbia University (US)
- Herbert Irving Comprehensive Cancer Center (US)
- Corresponding author
- Doetsch, Fiona
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 82
- Issue
- 3
- Pages
- 545-559
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4360885
- OpenAlex
- W2065970275
- Cited by
- 634
- References
- 88
- Citations by year
- 2026: 17 · 2025: 35 · 2024: 36 · 2023: 63 · 2022: 61 · 2021: 61 · 2020: 63 · 2019: 75 · 2018: 47 · 2017: 63 · 2016: 49 · 2015: 49 · 2014: 14
- FWCI
- 20.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- David and Lucile Packard Foundation
- Foundation for the National Institutes of Health
- Leona M. and Harry B. Helmsley Charitable Trust
- National Institutes of Health (TL1TR000082)
- National Institute of Mental Health (T32 MH 15174-29, T32MH015174)
- National Institute of General Medical Sciences (T32GM008224, T32GM007088)
- National Institute of Neurological Disorders and Stroke (F31NS081990, R01NS053884, NS074039, R01NS074039, NS053884, NS053884-03S109, F31NS079057)
- National Center for Advancing Translational Sciences
- 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 › Urology › Hair Growth and Disorders
- Keywords
- quiescent neural stem cells, ventricular-subventricular zone, stem cell activation, EGFR, nestin, olfactory bulb interneurons, stem cell quiescence, GPCR ligands, sphingosine-1-phosphate, prostaglandin D2, small molecule screening, colony-forming cells
- MeSH terms
- Animals, Astrocytes, Cell Separation, Cells, Cultured, Humans, Mice, Transgenic, Prospective Studies, Biomarkers, Lateral Ventricles, Mice, Adult Stem Cells, Neural Stem Cells, Transcriptome
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