Life-Long Neural Stem Cells Are Fate-Specified at an Early Developmental Stage

2020 ◽  
Vol 30 (12) ◽  
pp. 6415-6425
Author(s):  
Aoi Tanaka ◽  
Shohei Ishida ◽  
Takahiro Fuchigami ◽  
Yoshitaka Hayashi ◽  
Anri Kuroda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Olfactory Bulb ◽  
Neural Stem Cells ◽  
Integration Site ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Early Developmental Stage ◽  
Cell Cycle Time ◽  
Early Embryonic Stage ◽  
Early Developmental

Abstract The origin and life-long fate of quiescent neural stem cells (NSCs) in the adult mammalian brain remain largely unknown. A few neural precursor cells in the embryonic brain elongate their cell cycle time and subsequently become quiescent postnatally, suggesting the possibility that life-long NSCs are selected at an early embryonic stage. Here, we utilized a GFP-expressing lentivirus to investigate the fate of progeny from individual lentivirus-infected NSCs by identifying the lentiviral integration site. Our data suggest that NSCs become specified to two or more lineages prior to embryonic day 13.5 in mice: one NSC lineage produces cells only for the cortex and another provides neurons to the olfactory bulb. The majority of neurosphere-forming NSCs in the adult brain are relatively dormant and generate very few cells, if any, in the olfactory bulb or cortex, and this NSC population could serve as a reservoir that is occasionally reactivated later in life.

scholarly journals The Strange Case of Jekyll and Hyde: Parallels Between Neural Stem Cells and Glioblastoma-Initiating Cells

2021 ◽  
Vol 10 ◽  
Author(s):  
David Bakhshinyan ◽  
Neil Savage ◽  
Sabra Khalid Salim ◽  
Chitra Venugopal ◽  
Sheila K. Singh
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Current Therapies ◽  
Multipotent Differentiation ◽  
Radial Glial ◽  
Divergent Behavior ◽  
Genetic Profiles

During embryonic development, radial glial precursor cells give rise to neural lineages, and a small proportion persist in the adult mammalian brain to contribute to long-term neuroplasticity. Neural stem cells (NSCs) reside in two neurogenic niches of the adult brain, the hippocampus and the subventricular zone (SVZ). NSCs in the SVZ are endowed with the defining stem cell properties of self-renewal and multipotent differentiation, which are maintained by intrinsic cellular programs, and extrinsic cellular and niche-specific interactions. In glioblastoma, the most aggressive primary malignant brain cancer, a subpopulation of cells termed glioblastoma stem cells (GSCs) exhibit similar stem-like properties. While there is an extensive overlap between NSCs and GSCs in function, distinct genetic profiles, transcriptional programs, and external environmental cues influence their divergent behavior. This review highlights the similarities and differences between GSCs and SVZ NSCs in terms of their gene expression, regulatory molecular pathways, niche organization, metabolic programs, and current therapies designed to exploit these differences.

scholarly journals Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Kanako Nakaguchi ◽  
Hiroshi Masuda ◽  
Naoko Kaneko ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Ischemic Stroke ◽  
Neural Stem Cells ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Adult Brain ◽  
Neurological Deficits ◽  
Mammalian Brain ◽  
Striatal Neurons ◽  
Endogenous Neural Stem Cells

Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD) or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2251-2261 ◽  
Author(s):  
C.M. Morshead ◽  
C.G. Craig ◽  
D. van der Kooy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Olfactory Bulb ◽  
Neural Stem Cells ◽  
Anterior Commissure ◽  
Mammalian Brain ◽  
Proliferating Cells ◽  
Asymmetric Mode ◽  
Clone Size

The adult mammalian forebrain contains a population of multipotential neural stem cells in the subependyma of the lateral ventricles whose progeny are the constitutively proliferating cells, which divide actively throughout life. The adult mammalian brain is ideal for examining the kinetics of the stem cells due to their strict spatial localization and the limited and discrete type of progeny generated (constitutively proliferating cells). Clonal lineage analyses 6 days after retrovirus infection revealed that under baseline conditions 60% of the constitutively proliferating cells undergo cell death, 25% migrate to the olfactory bulb and 15% remain confined to the lateral ventricle subependyma (where they reside for approximately 15 days). Analysis of single cell clones 31 days after retroviral infection revealed that the stem cell divides asymmetrically to self-renew and give rise to constitutively proliferating cells. Following repopulation of the depleted subependyma the average clone size is 2.8 times larger than control, yet the absolute number of cells migrating to the olfactory bulb is maintained and the stem cell retains its asymmetric mode of division. The number of neural stem cells in the adult forebrain 33 days after repopulation of the subependyma was estimated using bromodeoxyuridine labeling of subepenydmal cells. There were calculated to be 1200–1300 cells between the rostral corpus callosum and rostral anterior commissure; these data support a lineage model similar to those based on stem cell behavior in other tissue types.

scholarly journals Neural stem cells: involvement in adult neurogenesis and CNS repair

2008 ◽  
Vol 363 (1500) ◽  
pp. 2111-2122 ◽  
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Adult Neurogenesis ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Therapeutic Interventions ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.

Human olfactory bulb neural stem cells mitigate movement disorders in a rat model of Parkinson's disease

2015 ◽  
Vol 230 (7) ◽  
pp. 1614-1629 ◽  
Author(s):  
Hany E.S. Marei ◽  
Samah Lashen ◽  
Amany Farag ◽  
Asmaa Althani ◽  
Nahla Afifi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Olfactory Bulb ◽  
Neural Stem Cells ◽  
Rat Model ◽  
Movement Disorders

scholarly journals Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

2020 ◽  
Author(s):  
JE Le Belle ◽  
J Sperry ◽  
K Ludwig ◽  
NG Harris ◽  
MA Caldwell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Olfactory Bulb ◽  
Neural Stem Cells ◽  
Egf Receptor ◽  
Brain Repair ◽  
Multipotent Stem Cells ◽  
Growth And Survival

AbstractFatty acids are well known as important constituents for the synthesis of membrane lipids and as sources of cellular energy in the CNS. However, fatty acids can also act as vital second messenger molecules in the nervous system and regulate the activity of many proteins affecting cell growth and survival. Here, we show that an essential dietary fatty acid, Decosahexaenoic acid, (DHA), can enhance stem cell function in vitro and in vivo. We found that this effect is not due to an increase in the overall proliferation rate of all neural progenitors, but is due to an increase in the number of multipotent stem cells that leads to greater levels of subventricular zone (SVZ) neurogenesis with restoration of olfactory function in aged mice. These effects were likely mediated through increased EGF-receptor sensitivity, a conversion of EGRFR+ progenitors back into an EGRFR+/GFAP+ stem cell state, and the activation of the PI3K/AKT signaling pathway, which is a critical pathway in many NSC cell functions including cell growth and survival. Together these data demonstrate that neural stem cells in the aged and quiescent neurogenic niche of the mouse SVZ retain their ability to self-renew and contribute to neurogenesis when apparently rejuvenated by DHA and PI3K/AKT pathway activation. DHA stimulation of this signaling enhances the number of multipotent stem cells and neurogenesis in young and aged rodent and human stem cells and hence may have implications for the manipulation of neural stem cells for brain repair.Significance StatementWe have identified potentially important effects of DHA on the stem cell population which may be unique to the SVZ stem cell niche. Our studies demonstrate that DHA can promote the production of neural stem cells, possibly via a non-proliferative mechanism stimulated by EGF receptor activation, and prolongs their viability. Aging animals undergo an apparent loss in SVZ stem cells and an associated decline in olfactory bulb function. We find that dietary DHA supplementation at least partially restores stem cell numbers, olfactory bulb neurogenesis and olfactory discrimination and memory in aged mice, demonstrating a capacity for rejuvenation is retained despite age-related changes to the niche, which has significant implications for ameliorating cognitive decline in aging and for endogenous brain repair.

scholarly journals Single cell 3’UTR analysis identifies changes in alternative polyadenylation throughout neuronal differentiation and in autism

2020 ◽  
Author(s):  
Manuel Göpferich ◽  
Nikhil Oommen George ◽  
Ana Domingo Muelas ◽  
Alex Bizyn ◽  
Rosa Pascual ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Single Cell ◽  
Neuronal Differentiation ◽  
Mrna Translation ◽  
Autism Spectrum ◽  
Adult Brain ◽  
Control Of Gene Expression ◽  
Risk Genes

SUMMARYAutism spectrum disorder (ASD) is a neurodevelopmental disease affecting social behavior. Many of the high-confident ASD risk genes relate to mRNA translation. Specifically, many of these genes are involved in regulation of gene expression for subcellular compartmentalization of proteins1. Cis-regulatory motifs that often localize to 3’- and 5’-untranslated regions (UTRs) offer an additional path for posttranscriptional control of gene expression. Alternative cleavage and polyadenylation (APA) affect 3’UTR length thereby influencing the presence or absence of regulatory elements. However, APA has not yet been addressed in the context of neurodevelopmental disorders. Here we used single cell 3’end sequencing to examine changes in 3’UTRs along the differentiation from neural stem cells (NSCs) to neuroblasts within the adult brain. We identified many APA events in genes involved in neurodevelopment, many of them being high confidence ASD risk genes. Further, analysis of 3’UTR lengths in single cells from ASD and healthy individuals detected longer 3’UTRs in ASD patients. Motif analysis of modulated 3’UTRs in the mouse adult neurogenic lineage and ASD-patients revealed enrichment of the cytoplasmic and polyadenylation element (CPE). This motif is bound by CPE binding protein 4 (CPEB4). In human and mouse data sets we observed co-regulation of CPEB4 and the CPEB-binding synaptic adhesion molecule amyloid beta precursor-like protein 1 (APLP1). We show that mice deficient in APLP1 show aberrant regulation of APA, decreased number of neural stem cells, and autistic-like traits. Our findings indicate that APA is used for control of gene expression along neuronal differentiation and is altered in ASD patients.

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