Maintenance of Neural Stem Cells in the Brain: Role of Notch Signaling

Abstract The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes–/–) mice. We found that the proliferation of Nes–/– neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes–/– mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.

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Neural Stem Cells: What Happens When They Go Viral?

Viruses ◽

10.3390/v13081468 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1468

Author(s):

Yashika S. Kamte ◽

Manisha N. Chandwani ◽

Alexa C. Michaels ◽

Lauren A. O’Donnell

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Viral Infections ◽

Wide Spectrum ◽

Cell Types ◽

Developmental Abnormalities ◽

Multipotent Progenitor Cells ◽

The Central Nervous System ◽

Simplex Virus ◽

The Brain

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

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Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

Journal of Oncology ◽

10.1155/2012/537861 ◽

2012 ◽

Vol 2012 ◽

pp. 1-20 ◽

Cited By ~ 17

Author(s):

Felipe de Almeida Sassi ◽

Algemir Lunardi Brunetto ◽

Gilberto Schwartsmann ◽

Rafael Roesler ◽

Ana Lucia Abujamra

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cellular Proliferation ◽

Survival Rates ◽

Comprehensive Analysis ◽

Heterogeneous Population ◽

Aggressive Tumor ◽

Epigenetic Modulation ◽

The Brain

Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.

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Mesenchymal stem cells regulate maintenance of neural stem cells through VEGFR2 and Notch signaling pathways

Cell Research ◽

10.1038/cr.2008.149 ◽

2008 ◽

Vol 18 (S1) ◽

pp. S59-S59

Author(s):

Zhifeng Deng ◽

Zhumin Liu ◽

Wei Tu ◽

Yang Wang ◽

Yuanlei Lou

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Neural Stem Cells ◽

Notch Signaling ◽

Signaling Pathways

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Tissue regeneration and repair in multiple sclerosis: the role of neural stem cells

Multiple Sclerosis ◽

10.1017/cbo9780511781698.008 ◽

2011 ◽

pp. 60-66

Author(s):

Stefano Pluchino ◽

Roberto Furlan ◽

Luca Muzio ◽

Gianvito Martino

Keyword(s):

Multiple Sclerosis ◽

Stem Cells ◽

Neural Stem Cells ◽

Tissue Regeneration

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The role of morphine on rat neural stem cells viability, neuro-angiogenesis and neuro-steroidgenesis properties

Neuroscience Letters ◽

10.1016/j.neulet.2016.11.025 ◽

2017 ◽

Vol 636 ◽

pp. 205-212 ◽

Cited By ~ 13

Author(s):

Nima Abdyazdani ◽

Alireza Nourazarian ◽

Hojjatollah Nozad Charoudeh ◽

Masoumeh Kazemi ◽

Navid Feizy ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells

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Rat Embryonic Cortical Neural Stem Cells: Role of Hypoxia on Cell Proliferation and Differentiation

Stem Cells and Cancer Stem Cells,Volume 3 ◽

10.1007/978-94-007-2415-0_6 ◽

2011 ◽

pp. 49-61

Author(s):

Yong Liu ◽

Haixia Lu ◽

Xinlin Chen

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Neural Stem Cells ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation

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SCIDOT-22. INTRACEREBROVENTRICULAR DELIVERY OF TUMOR-HOMING CYTOTOXIC HUMAN INDUCED NEURAL STEM CELLS FOR TREATMENT OF BRAIN METASTASES

Neuro-Oncology ◽

10.1093/neuonc/noz175.1158 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi276-vi276

Author(s):

Wulin Jiang ◽

Alison Mercer-Smith ◽

Juli Bago ◽

Simon Khagi ◽

Carey Anders ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Brain Metastases ◽

Neural Stem Cells ◽

Tumor Homing ◽

Migration Assays ◽

Induced Neural Stem Cells ◽

First Time ◽

The Brain

Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) and breast cancer are the most common cancers that metastasize to the brain. New therapies are needed to target and eradicate metastases. We have developed genetically-engineered induced neural stem cells (hiNSCs) derived from human fibroblasts that selectively home to tumors and release the cytotoxic protein TRAIL. Building on these results, we explored the efficacy of hiNSC therapy delivered via intracerebroventricular (ICV) injections for the treatment of metastatic foci in the brain for the first time. METHODS We performed in vitro efficacy and migration assays in conjunction with in vivo studies to determine the migration, persistence, and efficacy of therapeutic hiNSCs against H460 NSCLC and triple-negative breast cancer MB231-Br tumors in the brain. Following the establishment of tumors in the brains of nude mice, hiNSCs were injected directly into the tumor or the ventricle contralateral to the tumor. The migration and persistence of hiNSCs were investigated by following the bioluminescence of the hiNSCs. The therapeutic efficacy of the hiNSCs was determined by following the bioluminescence of the tumor. RESULTS/ CONCLUSION Co-culture results demonstrated that hiNSC therapy reduced the viability of H460 and MB231-Br up to 75% and 99.8% respectively compared to non-treated controls. In vitro migration assays showed significant directional migration toward both lung and breast cancer cells within 4 days. ICV-administered hiNSC serial imaging shows that cells persisted for >1 week in the brain. Fluorescent analysis of tissue sections showed that hiNSCs co-localized with lateral and contralateral tumors within 7 days. Using H460 and MB231-Br models, kinetic tracking of intracranial tumor volumes showed intratumoral or ICV-injected therapeutic hiNSCs suppressed the growth rate of brain tumors by 31-fold and 3-fold, respectively. This work demonstrates for the first time that we can effectively deliver personalized cytotoxic tumor-homing cells through the ventricles to target brain metastases.

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