Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain

Abstract

Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRβ) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRβ in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons. Together, our findings reveal that the adult V-SVZ contains spatial domains for gliogenesis, in addition to those for neurogenesis. These gliogenic NSC domains tend to be quiescent under homeostasis and may contribute to brain plasticity.

Zebrafish Vascular Mural Cell Biology: Recent Advances, Development, and Functions

“…Non-vascular-associated strong pdgfrb reporter expression is observable in the adult brain, including the stem cell niche area located at the cerebellum interface between the granule cell and molecular layers [ 35 ] ( Figure 1 D). PDGFRβ is reportedly expressed by neural stem cells in the adult mouse subventricular zone [ 36 ] as well as by human placental mesenchymal stem cells [ 37 ]. Thus, in addition to the established vascular biology, pdgfrb reporter zebrafish are also useful in a broad range of research fields.…”

miR-17∼92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

“…NSCs in the adult V-SVZ are heterogeneous at multiple levels, including their developmental origin (Fuentealba et al, 2015;Furutachi et al, 2015;Yuzwa et al, 2017), morphology (Delgado et al, 2021;Mirzadeh et al, 2008;Shen et al, 2008), regional position (reviewed in (Azim et al, 2016)) and response to physiological cues (Chaker et al, 2021;Paul et al, 2017). TACs are also heterogeneous with respect to their cell cycle dynamics and transcriptional signatures, which depends on their location (Azim et al, 2015;Ponti et al, 2013).…”

“…A list of genes expressed in early stages of the lineage was compiled from gene expression datasets of FACS-purified V-SVZ NSC populations (PDGFRβ + CD133 + , PDGFRβ + EGFR + and EGFR + ) (Delgado et al, 2021). Computationally predicted targets for the guide and star forms of individual members of the miR- 17~92 cluster (miR-17, 18a, 19a, 20a, 19b, 92a and miR-17*) were generated from the online platforms Targetscan, PicTar, microcosm and miRDB.…”

“…They are largely quiescent (qNSCs) and, upon activation (aNSCs), give rise to transit amplifying cells (TACs), which in turn generate neuroblasts that migrate to the olfactory bulb (OB) (Chaker et al, 2016;Obernier and Alvarez-Buylla, 2019). Importantly, NSCs also give rise to a small number of glial cells, including oligodendrocytes destined for the corpus callosum and intraventricular oligodendrocyte progenitor cells (OPCs) (Chaker et al, 2016;Delgado et al, 2021;Obernier and Alvarez-Buylla, 2019).…”

Isolation of neural stem and oligodendrocyte progenitor cells from the brain of live rats

“…Our data revealed that culture medium conditioned with choroid plexus factors induced the proliferation of isolated cells, as expected based on previous reports ( Silva-Vargas et al., 2016 ), but at the same time significantly decreased their self-renewal capacity. In a recent paper, platelet-derived growth factor D has been identified as a component of the CSF that acts via PDGFRβ to enhance quiescence of NSCs ( Delgado et al., 2021 ). By transferring the targeted area of the ventricular wall more caudally and away from the SEZ niche, we were able to isolate cells with typical OPC marker profile.…”