Characterization of neuroprogenitor cells expressing the PDGF β-receptor within the subventricular zone of postnatal mice

Ikoma, Yoko; Matsumoto, Yoshiki; Watanabe, Rie; Elmi, Muna; Fujimori, Toshihiko; Nissen, Johan; Cao, Yihai; Nabeshima, Yo‐ichi; Sasahara, Masakiyo; Funa, Keiko

doi:10.1016/j.mcn.2007.11.006

Cited by 53 publications

(46 citation statements)

References 44 publications

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“…Some studies have suggested that neuronal progenitor cells (NPCs) in the subventricular zone also express PDGRFβ [40], but studies by others in the embryonic CNS [7], adult CNS [11, 31] or in acutely isolated murine neurons [41] did not confirm these findings. Relevant to this study, however, is also that NPCs do not normally reside in the presently studied brain regions including cortex, hippocampus or thalamus.…”

Section: Discussionmentioning

confidence: 99%

Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling

et al. 2017

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Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain. We asked whether these mice have a stable or progressive vascular phenotype after birth, and whether both pericyte and VSMCs populations are affected in the adult brain. We found an early and progressive region-dependent loss of brain pericytes, microvascular reductions and blood-brain barrier (BBB) breakdown, which were more pronounced in the cortex, hippocampus and striatum than in the thalamus, whereas VSMCs population remained unaffected at the time when pericyte loss was already established. For example, compared to age-matched controls, PdgfrβF7/F7 mice between 4–6 and 36–48 weeks of age developed a region-dependent loss in pericyte coverage (22–46, 24–44 and 4–31%) and cell numbers (36–49, 34–64 and 11–36%), reduction in capillary length (20–39, 13–46 and 1–30%), and an increase in extravascular fibrinogen-derived deposits (3.4–5.2, 2.8–4.1 and 0–3.6-fold) demonstrating BBB breakdown in the cortex, hippocampus and thalamus, respectively. Capillary reductions and BBB breakdown correlated with loss of pericyte coverage. Our data suggest that PdgfrβF7/F7 mice develop an aggressive and rapid vascular phenotype without appreciable early involvement of VSMCs, therefore providing a valuable model to study regional effects of pericyte loss on brain vascular and neuronal functions. This model could be a useful tool for future studies directed at understanding the role of pericytes in the pathogenesis of neurological disorders associated with pericyte loss such as vascular dementia, Alzheimer’s disease, amyotrophic lateral sclerosis, stroke and human immunodeficiency virus-associated neurocognitive disorder.

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Section: Discussionmentioning

confidence: 99%

Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling

et al. 2017

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“…We have used hGFAP::GFP mice to identify B1 cells and immunostaining for Ascl1 and DCX to label C and A cells, respectively (23,26,45). Most of the proliferating hGFAP::GFP + astrocytes within the V-SVZ are neural stem cells (1,46) and express other astrocytic markers, such as Glutamate Aspartate Transporter (GLAST) (47) and Aldehyde dehydrogenase family 1 member L1 (Aldh1-L1)L1 (48). hGFAP::GFP mice reporter protein was more reliable for quantification of B1 cells than GLAST::DsRed (49) and AldH1-L1::GFP (50) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice

Ponti

Obernier

Guinto

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

238

212

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“…Within the CNS, PDGF maintains neural stem cells (NSCs) with differential receptor expression based on developmental stage. Ishii et al (2008) reported that NSCs located in the subventricular zone (SVZ) of an early postnatal mouse brain express PDGFRb and that PDGFRb-mediated signaling is not essential for ex vivo NSC proliferation, but rather their survival, migration, and neural differentiation (Ishii et al 2008). However, this same group (Ishii et al 2006) demonstrated that a brain-specific disruption of PDGFRb using a nestin-Cre model displayed grossly normal development, but with cognitive and socio-emotional deficits (Nguyen et al 2011) and hippocampal neuronal dendrite alterations (Shioda et al 2011).…”

mentioning

confidence: 99%

Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity

Kim¹,

Kim²,

Wu³

et al. 2012

Genes Dev.

116

101

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Growth factor-mediated proliferation and self-renewal maintain tissue-specific stem cells and are frequently dysregulated in cancers. Platelet-derived growth factor (PDGF) ligands and receptors (PDGFRs) are commonly overexpressed in gliomas and initiate tumors, as proven in genetically engineered models. While PDGFRa alterations inform intertumoral heterogeneity toward a proneural glioblastoma (GBM) subtype, we interrogated the role of PDGFRs in intratumoral GBM heterogeneity. We found that PDGFRa is expressed only in a subset of GBMs, while PDGFRb is more commonly expressed in tumors but is preferentially expressed by self-renewing tumorigenic GBM stem cells (GSCs). Genetic or pharmacological targeting of PDGFRb (but not PDGFRa) attenuated GSC self-renewal, survival, tumor growth, and invasion. PDGFRb inhibition decreased activation of the cancer stem cell signaling node STAT3, while constitutively active STAT3 rescued the loss of GSC selfrenewal caused by PDGFRb targeting. In silico survival analysis demonstrated that PDGFRB informed poor prognosis, while PDGFRA was a positive prognostic factor. Our results may explain mixed clinical responses of anti-PDGFR-based approaches and suggest the need for integration of models of cancer as an organ system into development of cancer therapies.

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Characterization of neuroprogenitor cells expressing the PDGF β-receptor within the subventricular zone of postnatal mice

Cited by 53 publications

References 44 publications

Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling

Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling

Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice

Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity

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