scholarly journals Persistent Cyfip1 expression is required to maintain the adult subventricular zone neurogenic niche

2019 ◽  
Author(s):  
Christa Whelan Habela ◽  
Ki-Jun Yoon ◽  
Namshik Kim ◽  
Arens Taga ◽  
Kassidy Bell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Critical Role ◽  
Interacting Protein ◽  
Embryonic Mouse ◽  
Lateral Ventricles ◽  
Ventricular Surface ◽  
Adult Nscs ◽  
B1 Cells

ABSTRACTNeural stem cells (NSCs) persist throughout life in the subventricular zone (SVZ) niche of the lateral ventricles as B1 cells. Maintaining this population of NSCs depends on the balance between quiescence and self-renewing or self-depleting proliferation. Interactions between B1 cells and the surrounding niche are important in regulating this balance, but the mechanisms governing these processes have not been fully elucidated in adult mammals. The cytoplasmic FMRP-interacting protein (CYFIP1) regulates apical-basal polarity in the embryonic brain. Loss of Cyfip1 during embryonic development in mice disrupts the embryonic niche and affects cortical neurogenesis. However, a direct role for Cyfip1 in the regulation of adult NSCs has not been established. Here, we demonstrate that Cyfip1 expression is preferentially localized to B1 cells in the adult SVZ. Loss of Cyfip1 in the embryonic mouse brain results in altered adult SVZ architecture and expansion of the adult B1 cell population at the ventricular surface. Furthermore, acute deletion of Cyfip1 in adult NSCs results in a rapid change in adherens junction proteins as well as increased proliferation and the number of B1 cells at the ventricular surface. Together, these data indicate that CYFIP1 plays a critical role in the formation and maintenance of the adult SVZ niche and, furthermore, deletion of Cyfip1 unleashes the capacity of adult B1 cells for symmetric renewal to increase the adult NSC pool.SIGNIFICANCENeural stem cells (NSCs) persist in the subventricular zone (SVZ) of the lateral ventricles in adult mammals and their population is determined by the balance between quiescence and self-depleting or renewing cell division. The mechanisms regulating their biology are not fully understood. This study establishes that the cytoplasmic FMRP interacting protein 1 (Cyfip1) regulates NSC fate decisions in the adult SVZ and NSCs that are quiescent or typically undergo self-depleting divisions retain the ability to self-renew in the adult. This contributes to our understanding of how adult NSCs are regulated throughout life and has potential implications for human brain disorders.

scholarly journals Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice

2016 ◽  
Vol 27 (4) ◽  
pp. 627-639 ◽  
Author(s):  
Qiong Zhou ◽  
Edwin A. Obana ◽  
Kryslaine L. Radomski ◽  
Gauthaman Sukumar ◽  
Christopher Wynder ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Intracellular Transport ◽  
Culture Conditions ◽  
Histone Demethylase ◽  
Proximal Promoter ◽  
Expression Screening ◽  
Adult Nscs ◽  
Transcriptional Changes

The role of epigenetic regulators in the control of adult neurogenesis is largely undefined. We show that the histone demethylase enzyme Kdm5b (Jarid1b) negatively regulates neurogenesis from adult subventricular zone (SVZ) neural stem cells (NSCs) in culture. shRNA-mediated depletion of Kdm5b in proliferating adult NSCs decreased proliferation rates and reduced neurosphere formation in culture. When transferred to differentiation culture conditions, Kdm5b-depleted adult NSCs migrated from neurospheres with increased velocity. Whole-genome expression screening revealed widespread transcriptional changes with Kdm5b depletion, notably the up-regulation of reelin ( Reln), the inhibition of steroid biosynthetic pathway component genes and the activation of genes with intracellular transport functions in cultured adult NSCs. Kdm5b depletion increased extracellular reelin concentration in the culture medium and increased phosphorylation of the downstream reelin signaling target Disabled-1 (Dab1). Sequestration of extracellular reelin with CR-50 reelin-blocking antibodies suppressed the increase in migratory velocity of Kdm5b-depleted adult NSCs. Chromatin immunoprecipitation revealed that Kdm5b is present at the proximal promoter of Reln, and H3K4me3 methylation was increased at this locus with Kdm5b depletion in differentiating adult NSCs. Combined the data suggest Kdm5b negatively regulates neurogenesis and represses Reln in neural stem cells from the adult SVZ.

scholarly journals Subventricular zone adult mouse neural stem cells and human glioblastoma stem cells require insulin receptor for self-renewal

2020 ◽  
Author(s):  
Shravanthi Chidambaram ◽  
Deborah Rothbard ◽  
Kaivalya Deshpande ◽  
Yvelanda Cajuste ◽  
Kristin M. Snyder ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Insulin Receptor ◽  
Subventricular Zone ◽  
High Ratio ◽  
Hippocampal Neurogenesis ◽  
Self Renewal ◽  
Pathway Gene ◽  
Evolutionarily Conserved ◽  
Adult Nscs

SummaryThe insulin receptor (IR) is an evolutionarily conserved signaling protein that regulates development and cellular metabolism. IR signaling regulates neurogenesis in Drosophila; however, a specific role for the IR in maintaining adult neural stem cells (NSCs) in mammals has not been investigated. We show that conditionally deleting the IR reduces adult NSCs of the subventricular zone by ∼70% accompanied by a corresponding increase in progenitors. IR deletion produced hyposmia due to aberrant olfactory bulb neurogenesis. Interestingly, hippocampal neurogenesis was not perturbed nor were hippocampal dependent behaviors. Highly aggressive proneural and mesenchymal glioblastomas (GBMs) had high IR/insulin-like growth factor (IGF) pathway gene expression, and isolated glioma stem cells had an aberrantly high ratio of IR:IGF1R receptors. Moreover, IR knockdown inhibited proneural and mesenchymal GBM tumorsphere growth. Altogether, these data demonstrate that the IR is essential for a subset of normal NSCs as well as for brain tumor cancer stem cell self-renewal.

Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells

2011 ◽  
Vol 89 (8) ◽  
pp. 1185-1193 ◽  
Author(s):  
Gadi Turgeman ◽  
Adi Pinkas ◽  
Theodore A. Slotkin ◽  
Matanel Tfilin ◽  
Rachel Langford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone

Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice

2017 ◽  
Vol 222 (6) ◽  
pp. 2855-2876 ◽  
Author(s):  
Valentina Mastrorilli ◽  
Chiara Scopa ◽  
Daniele Saraulli ◽  
Marco Costanzi ◽  
Raffaella Scardigli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Physical Exercise ◽  
Neural Stem Cells ◽  
Knockout Mice ◽  
Subventricular Zone

scholarly journals Neuroprotective effects of dexmedetomidine on the ketamine-induced disruption of the proliferation and differentiation of developing neural stem cells in the subventricular zone

2020 ◽  
Author(s):  
Huanhuan Sha ◽  
Peipei Peng ◽  
Bing Li ◽  
Guohua Wei ◽  
Juan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Pediatric Anesthesia ◽  
Brdu Incorporation ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Proliferation And Differentiation ◽  
Ketamine Anesthesia ◽  
Β Tubulin

Abstract Background: Recently, the number of neonatal patients receiving surgery under general anesthesia has increased. Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and the children’s parents. Dexmedetomidine (DEX) is widely used in sedation, as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following 5 groups: Control group (n=8), Ketamine group (n=8), 1 μg/kg DEX+Ketamine group (n=8), 5 μg/kg DEX+Ketamine group (n=8) and 10 μg/kg DEX+Ketamine group (n=8). The proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining with BrdU incorporation. The levels of Nestin and β-tubulin III in the SVZ were measured using Western blot analyses. Apoptosis was assessed by detecting the levels of the cleaved caspase-3 protein using Western blotting. Results: Neonatal ketamine exposure significantly inhibited NSC proliferation and astrocytic differentiation in the SVZ, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderate (5 μg/kg) or high doses (10 μg/kg) of DEX reversed the ketamine-induced disturbances in the proliferation and differentiation of NSCs. Meanwhile, neonatal ketamine exposure significantly decreased the expression of Nestin and increased the expression of β-tubulin III in the SVZ compared with the Control group. Treatment with 10 μg/kg DEX notably reversed the ketamine-induced changes in the levels of Nestin and β-tubulin III. In addition, a pretreatment with 10 μg/kg DEX before ketamine anesthesia prevented apoptosis in the SVZ induced by neonatal ketamine exposure. Conclusions: Based on our findings, DEX may exert neuroprotective effects on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in a repeated ketamine anesthesia model.

scholarly journals Egr-1 is a Critical Regulator of EGF-Receptor-Mediated Expansion of Subventricular Zone Neural Stem Cells and Progenitors During Recovery from Hypoxia–Hypoglycemia

ASN NEURO ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. AN20120032 ◽  
Author(s):  
Dhivyaa Alagappan ◽  
Murugabaskar Balan ◽  
Yuhui Jiang ◽  
Rachel B. Cohen ◽  
Sergei V. Kotenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Egf Receptor

scholarly journals Differentiation Induction as a Response to Irradiation in Neural Stem Cells In Vitro

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 913 ◽  
Author(s):  
Jana Konířová ◽  
Lukáš Cupal ◽  
Šárka Jarošová ◽  
Anna Michaelidesová ◽  
Jana Vachelová ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Cancer ◽  
Subventricular Zone ◽  
Transcriptional Activity ◽  
Radiation Induced ◽  
Induction Of Differentiation ◽  
Stem Cell Populations ◽  
Neurocognitive Decline

Radiotherapy plays a significant role in brain cancer treatment; however, the use of this therapy is often accompanied by neurocognitive decline that is, at least partially, a consequence of radiation-induced damage to neural stem cell populations. Our findings describe features that define the response of neural stem cells (NSCs) to ionizing radiation. We investigated the effects of irradiation on neural stem cells isolated from the ventricular-subventricular zone of mouse brain and cultivated in vitro. Our findings describe the increased transcriptional activity of p53 targets and proliferative arrest after irradiation. Moreover, we show that most cells do not undergo apoptosis after irradiation but rather cease proliferation and start a differentiation program. Induction of differentiation and the demonstrated potential of irradiated cells to differentiate into neurons may represent a mechanism whereby damaged NSCs eliminate potentially hazardous cells and circumvent the debilitating consequences of cumulative DNA damage.

scholarly journals Neural Stem Cells in the Subventricular Zone are Resilient to Hypoxia/Ischemia whereas Progenitors are Vulnerable

2004 ◽  
Vol 24 (7) ◽  
pp. 814-825 ◽  
Author(s):  
Michael J. Romanko ◽  
Raymond P. Rothstein ◽  
Steven W. Levison
Keyword(s):  
Electron Microscopy ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Caspase 3 ◽  
Hybrid Cell ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Neurologic Disability ◽  
Hematoxylin And Eosin ◽  
Dying Cells

Perinatal hypoxic-ischemic (H/I) brain injury remains a major cause of neurologic disability. Because we have previously demonstrated that this insult depletes cells from the subventricular zone (SVZ), the goal of the present investigation was to compare the relative vulnerability to H/I of neural stem cells versus progenitors. The dorsolateral SVZs of P6 rats were examined at 2 to 48 hours of recovery from H/I using hematoxylin and eosin, in situ end labeling (ISEL), terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL), electron microscopy, and immunofluorescence. Pyknotic nuclei and ISEL+ cells were observed by 4 hours of recovery, peaked at 12 hours, and persisted for at least 48 hours. Many active-caspase3+ cells were observed at 12 hours and they comprised one third of the total TUNEL+ population. Electron microscopy revealed that hybrid cell deaths predominated at 12 hours of recovery. Importantly, few dying cells were observed in the medial SVZ, where putative stem cells reside, and no nestin+ medial SVZ cells showed caspase-3 activation. By contrast, active-caspase-3+/PSA-NCAM+ progenitors were prominent in the lateral SVZ. These data demonstrate that early progenitors are vulnerable to H/I, whereas neural stem cells are resilient. The demise of these early progenitors may lead to the depletion of neuronal and late oligodendrocyte progenitors, contributing to cerebral dysgenesis after perinatal insults.

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