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Xiwei Shan, Lyl Tomlinson, Qian Yang, Holly Colognato
The regulatory mechanisms that control neural stem cell (NSC) activation in the adult ventricular-subventricular zone (V-SVZ) stem cell niche have been the focus of intense investigation, yet how the niche first develops and organizes is poorly understood. Here, we examined matrix metalloproteinases (MMPs) for potential roles in V-SVZ stem cell niche development. MMP12 was found to promote appropriate niche cellular arrangements, the formation of specialized niche extracellular matrix, and the translational planar cell polarity of ependymal cells that surround and support niche NSCs...
February 28, 2018: Stem Cell Reports
Kirsten Obernier, Arantxa Cebrian-Silla, Matthew Thomson, José Ignacio Parraguez, Rio Anderson, Cristina Guinto, José Rodas Rodriguez, José-Manuel Garcia-Verdugo, Arturo Alvarez-Buylla
Somatic stem cells have been identified in multiple adult tissues. Whether self-renewal occurs symmetrically or asymmetrically is key to understanding long-term stem cell maintenance and generation of progeny for cell replacement. In the adult mouse brain, neural stem cells (NSCs) (B1 cells) are retained in the walls of the lateral ventricles (ventricular-subventricular zone [V-SVZ]). The mechanism of B1 cell retention into adulthood for lifelong neurogenesis is unknown. Using multiple clonal labeling techniques, we show that the vast majority of B1 cells divide symmetrically...
February 1, 2018: Cell Stem Cell
Anna Engler, Chiara Rolando, Claudio Giachino, Ichiko Saotome, Andrea Erni, Callum Brien, Runrui Zhang, Ursula Zimber-Strobl, Freddy Radtke, Spyros Artavanis-Tsakonas, Angeliki Louvi, Verdon Taylor
Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis...
January 23, 2018: Cell Reports
Hideo Jinnou, Masato Sawada, Koya Kawase, Naoko Kaneko, Vicente Herranz-Pérez, Takuya Miyamoto, Takumi Kawaue, Takaki Miyata, Yasuhiko Tabata, Toshihiro Akaike, José Manuel García-Verdugo, Itsuki Ajioka, Shinji Saitoh, Kazunobu Sawamoto
Radial glia (RG) are embryonic neural stem cells (NSCs) that produce neuroblasts and provide fibers that act as a scaffold for neuroblast migration during embryonic development. Although they normally disappear soon after birth, here we found that RG fibers can persist in injured neonatal mouse brains and act as a scaffold for postnatal ventricular-subventricular zone (V-SVZ)-derived neuroblasts that migrate to the lesion site. This injury-induced maintenance of RG fibers has a limited time window during post-natal development and promotes directional saltatory movement of neuroblasts via N-cadherin-mediated cell-cell contacts that promote RhoA activation...
December 14, 2017: Cell Stem Cell
Francisco Fernández-Flores, José Manuel García-Verdugo, Raquel Martín-Ibáñez, Cristina Herranz, Dolors Fondevila, Josep María Canals, Carles Arús, Martí Pumarola
The mammalian ventricular-subventricular zone (V-SVZ) presents the highest neurogenic potential in the brain of the adult individual. In rodents, it is mainly composed of chains of neuroblasts. In humans, it is organized in layers where neuroblasts do not form chains. The aim of this study is to describe the cytoarchitecture of canine V-SVZ (cV-SVZ), to assess its neurogenic potential, and to compare our results with those previously described in other species. We have studied by histology, immunohistochemistry (IHC), electron microscopy and neurosphere assay the morphology, cytoarchitecture and neurogenic potential of cV-SVZ...
March 1, 2018: Journal of Comparative Neurology
Maria Apostolopoulou, Thomas R Kiehl, Mark Winter, Edgar Cardenas De La Hoz, Nathan C Boles, Christopher S Bjornsson, Kristen L Zuloaga, Susan K Goderie, Yue Wang, Andrew R Cohen, Sally Temple
Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18, and 22 months, we found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1(+) progenitor cells decreased in number and proliferation between 2 and 18 months but increased between 18 and 22 months...
November 8, 2017: Stem Cell Reports
Justine Sinnaeve, Bret C Mobley, Rebecca A Ihrie
Increasing evidence indicates that the adult neurogenic niche of the ventricular-subventricular zone (V-SVZ), beyond serving as a potential site of origin, affects the outcome of malignant brain cancers. Glioma contact with this niche predicts worse prognosis, suggesting a supportive role for the V-SVZ environment in tumor initiation or progression. In this review, we describe unique components of the V-SVZ that may permit or promote tumor growth within the region. Cell-cell interactions, soluble factors, and extracellular matrix composition are discussed, and the role of the niche in future therapies is explored...
January 2018: American Journal of Pathology
Jiwen Li, Chunyang Wang, Zhuangzhi Zhang, Yan Wen, Lei An, Qifei Liang, Zhejun Xu, Song Wei, Weiwei Li, Teng Guo, Guoping Liu, Guangxu Tao, Yan You, Heng Du, Zhuoning Fu, Miao He, Bin Chen, Kenneth Campbell, Arturo Alvarez-Buylla, John L Rubenstein, Zhengang Yang
Neural stem cells in the postnatal telencephalic ventricular-subventricular zone (V-SVZ) generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) into the olfactory bulb (OB). The Sp8 and Sp9 transcription factors are expressed in neuroblasts, as well as in the immature and mature interneurons in the V-SVZ-RMS-OB system. Here we show that Sp8 and Sp9 coordinately regulate OB interneuron development: although Sp9 null mutants show no major OB interneuron defect, conditional deletion of both Sp8 and Sp9 resulted in a much more severe reduction of OB interneuron number than that observed in the Sp8 conditional mutant mice, due to defects in neuronal differentiation, tangential and radial migration, and increased cell death in the V-SVZ-RMS-OB system...
August 1, 2017: Cerebral Cortex
Deana M Apple, Erzsebet Kokovay
Neural stem cells (NSCs) persist throughout life in the dentate gyrus and the ventricular-subventricular zone, where they continuously provide new neurons and some glia. These cells are found in specialized niches that regulate quiescence, activation, differentiation, and cell fate choice. A key aspect of the regulatory niche is the vascular plexus, which modulates NSC behavior during tissue homeostasis and regeneration. During aging, NSCs become depleted and dysfunctional, resulting in reduced neurogenesis and poor brain repair...
November 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Xiao-Ling Hu, Guo Chen, Sanguo Zhang, Jiangli Zheng, Jun Wu, Qing-Ran Bai, Yue Wang, Ji Li, Huanhuan Wang, Han Feng, Jia Li, Xicai Sun, Qijun Xia, Fan Yang, Jing Hang, Chang Qi, Timothy N Phoenix, Sally Temple, Qin Shen
During development, neural stem cells (NSCs) undergo transitions from neuroepithelial cells to radial glial cells (RGCs), and later, a subpopulation of slowly dividing RGCs gives rise to the quiescent adult NSCs that populate the ventricular-subventricular zone (V-SVZ). Here we show that VCAM1, a transmembrane protein previously found in quiescent adult NSCs, is expressed by a subpopulation of embryonic RGCs, in a temporal and region-specific manner. Loss of VCAM1 reduced the number of active embryonic RGCs by stimulating their premature neuronal differentiation while preventing quiescence in the slowly dividing RGCs...
July 19, 2017: Neuron
Arantxa Cebrián-Silla, Clara Alfaro-Cervelló, Vicente Herranz-Pérez, Naoko Kaneko, Dae Hwi Park, Kazunobu Sawamoto, Arturo Alvarez-Buylla, Daniel A Lim, José Manuel García-Verdugo
Neural stem cells (B1 astrocytes; NSCs) in the adult ventricular-subventricular-zone (V-SVZ) originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS), reported in certain lymphocytes and some cancer cells...
July 11, 2017: Stem Cell Reports
Deana M Apple, Rene Solano-Fonseca, Erzsebet Kokovay
Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair...
October 1, 2017: Biochemical Pharmacology
Alex Paul, Zayna Chaker, Fiona Doetsch
Neural stem cells (NSCs) in specialized niches in the adult mammalian brain generate neurons throughout life. NSCs in the adult mouse ventricular-subventricular zone (V-SVZ) exhibit a regional identity and, depending on their location, generate distinct olfactory bulb interneuron subtypes. Here, we show that the hypothalamus, a brain area regulating physiological states, provides long-range regionalized input to the V-SVZ niche and can regulate specific NSC subpopulations. Hypothalamic proopiomelanocortin neurons selectively innervate the anterior ventral V-SVZ and promote the proliferation of Nkx2...
June 30, 2017: Science
Gabrielle Rushing, Rebecca A Ihrie
BACKGROUND: The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease...
August 2016: Frontiers in Biology
Naoko Kaneko, Masato Sawada, Kazunobu Sawamoto
Adult neurogenesis was first observed nearly 60 years ago, and it has since grown into an important neurochemistry research field. Much recent research has focused on the treatment of brain diseases through neuronal regeneration with endogenously generated neurons. In the adult brain, immature neurons called neuroblasts are continuously generated in the ventricular-subventricular zone (V-SVZ). These neuroblasts migrate rapidly through the rostral migratory stream to the olfactory bulb, where they mature and are integrated into the neuronal circuitry...
June 2017: Journal of Neurochemistry
Christina Kyrousi, Zoi Lygerou, Stavros Taraviras
The V-SVZ adult neurogenic niche is located in the wall of the lateral ventricles and contains neural stem cells, with self-renewing and differentiating ability and postmitotic multiciliated ependymal cells, an important structural and trophic component of the niche. The niche is established at postnatal stages from a subpopulation of radial glial cells, determined during embryogenesis. Radial glial cells constitute a heterogeneous population, which give rise, in addition to niche cellular components, to neurons and glial cells...
February 7, 2017: Glia
Joanne C Conover, Krysti L Todd
In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear...
August 2017: Experimental Gerontology
Mathieu Daynac, Linda Tirou, Hélène Faure, Marc-André Mouthon, Laurent R Gauthier, Heidi Hahn, François D Boussin, Martial Ruat
Identifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs) is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh) signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zone (V-SVZ), one of the main brain neurogenic niches. Specific deletion of the Hh receptor Patched in NSCs during adulthood upregulated Hh signaling in quiescent NSCs, progressively leading to a large accumulation of these cells in the V-SVZ...
October 11, 2016: Stem Cell Reports
Zayna Chaker, Paolo Codega, Fiona Doetsch
Neural stem cells (NSCs) reside in specialized niches in the adult mammalian brain. The ventricular-subventricular zone (V-SVZ), adjacent to the lateral ventricles, gives rise to olfactory bulb (OB) neurons, and some astrocytes and oligodendrocytes throughout life. In vitro assays have been widely used to retrospectively identify NSCs. However, cells that behave as stem cells in vitro do not reflect the identity, diversity, and behavior of NSCs in vivo. Novel tools including fluorescence activated cell sorting, lineage-tracing, and clonal analysis have uncovered multiple layers of adult V-SVZ NSC heterogeneity, including proliferation state and regional identity...
November 2016: Wiley Interdisciplinary Reviews. Developmental Biology
Akshitkumar M Mistry, Andrew T Hale, Lola B Chambless, Kyle D Weaver, Reid C Thompson, Rebecca A Ihrie
The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV-GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV-GBM patients were identified...
January 2017: Journal of Neuro-oncology
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