Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche

By P. Codega, V. Silva-Vargas, Alex Paul, Angel R. Maldonado-Soto, A. DeLeo, Érika Pastrana, F. Doetsch. Neuron, 2014

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SUMMARY 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.

Subfields: Developmental Neuroscience, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9f508364d0c47d02981057a34c27882ff00090de

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Citations in the corpus

Toward Minimal Residual Disease-Directed Therapy in Melanoma. (2018, unknown): “Consistently, GSEA identified significant similarities between the NCSC signature and quiescent neural stem cell profiles (Codega et al., 2014; Llorens-Bobadilla et al., 2015), as well as with other cancer stem cell profiles (Figures 5A, S5A, and S5B).”
Single-cell RNA-seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis (2015, methodology): “…of adult neurogenesis in vivo, we Cell S used a transgenic mouse line that expresses nucleus-localized CFP under the Nestin regulatory elements (Nes-CFPnuc) (Encinas et al., 2006), in which CFP proteins carry over from adult qNSCs to their immediate progeny (collectively named NPCs; Figure S1A).”
Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury. (2015, unknown): “…largely overlaps with that GFAP (Beckervordersandforth et al., 2010; Codega et al., 2014; Platel et al., 2009), and reporter expression of hGFAP-GFP together with Prom1 has been used tomark and extract SVZNSCs (Beckervordersandforth et al., 2010; Codega et al., 2014; Mirzadeh et al., 2008).”
Single-Cell Profiling and SCOPE-Seq Reveal Lineage Dynamics of Adult Ventricular-Subventricular Zone Neurogenesis and NOTUM as a Key Regulator (2020, methodology): “The V-SVZ contains both quiescent neural stem cells (qNSCs) and actively dividing neural stem cells (aNSCs) (Codega et al., 2014; Mich et al., 2014), with intrinsic regional identities defined during embryogenesis (Fuentealba et al.”