scholarly journals Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

2019 ◽  
Author(s):  
Tamsin J. Samuels ◽  
Aino I. Järvelin ◽  
David Ish-Horowicz ◽  
Ilan Davis
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Mrna Stability ◽  
Rna Binding ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Protein Levels ◽  
The Brain

ABSTRACTThe numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by known extrinsic signals. However, the intrinsic mechanisms that control the characteristic proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, while heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.Abstract Figure

scholarly journals Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tamsin J Samuels ◽  
Aino I Järvelin ◽  
David Ish-Horowicz ◽  
Ilan Davis
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Mrna Stability ◽  
Rna Binding ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Protein Levels ◽  
The Brain

The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.

scholarly journals Histone Demethylase LSD1 Regulates Neural Stem Cell Proliferation

2010 ◽  
Vol 30 (8) ◽  
pp. 1997-2005 ◽  
Author(s):  
GuoQiang Sun ◽  
Kamil Alzayady ◽  
Richard Stewart ◽  
Peng Ye ◽  
Su Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Target Genes ◽  
Neural Progenitor ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Cell Proliferation Inhibition

ABSTRACT Lysine-specific demethylase 1 (LSD1) functions as a transcriptional coregulator by modulating histone methylation. Its role in neural stem cells has not been studied. We show here for the first time that LSD1 serves as a key regulator of neural stem cell proliferation. Inhibition of LSD1 activity or knockdown of LSD1 expression led to dramatically reduced neural stem cell proliferation. LSD1 is recruited by nuclear receptor TLX, an essential neural stem cell regulator, to the promoters of TLX target genes to repress the expression of these genes, which are known regulators of cell proliferation. The importance of LSD1 function in neural stem cells was further supported by the observation that intracranial viral transduction of the LSD1 small interfering RNA (siRNA) or intraperitoneal injection of the LSD1 inhibitors pargyline and tranylcypromine led to dramatically reduced neural progenitor proliferation in the hippocampal dentate gyri of wild-type adult mouse brains. However, knockout of TLX expression abolished the inhibitory effect of pargyline and tranylcypromine on neural progenitor proliferation, suggesting that TLX is critical for the LSD1 inhibitor effect. These findings revealed a novel role for LSD1 in neural stem cell proliferation and uncovered a mechanism for neural stem cell proliferation through recruitment of LSD1 to modulate TLX activity.

scholarly journals Adenosine kinase inhibition promotes proliferation of neural stem cells after traumatic brain injury

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Hoda M Gebril ◽  
Rizelle Mae Rose ◽  
Raey Gesese ◽  
Martine P Emond ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Brain Injury ◽  
Neural Stem Cell ◽  
Adenosine Kinase ◽  
Health Concern ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
The Brain

Abstract Traumatic brain injury (TBI) is a major public health concern and remains a leading cause of disability and socio-economic burden. To date, there is no proven therapy that promotes brain repair following an injury to the brain. In this study, we explored the role of an isoform of adenosine kinase expressed in the cell nucleus (ADK-L) as a potential regulator of neural stem cell proliferation in the brain. The rationale for this hypothesis is based on coordinated expression changes of ADK-L during foetal and postnatal murine and human brain development indicating a role in the regulation of cell proliferation and plasticity in the brain. We first tested whether the genetic disruption of ADK-L would increase neural stem cell proliferation after TBI. Three days after TBI, modelled by a controlled cortical impact, transgenic mice, which lack ADK-L (ADKΔneuron) in the dentate gyrus (DG) showed a significant increase in neural stem cell proliferation as evidenced by significant increases in doublecortin and Ki67-positive cells, whereas animals with transgenic overexpression of ADK-L in dorsal forebrain neurons (ADK-Ltg) showed an opposite effect of attenuated neural stem cell proliferation. Next, we translated those findings into a pharmacological approach to augment neural stem cell proliferation in the injured brain. Wild-type C57BL/6 mice were treated with the small molecule adenosine kinase inhibitor 5-iodotubercidin for 3 days after the induction of TBI. We demonstrate significantly enhanced neural stem cell proliferation in the DG of 5-iodotubercidin-treated mice compared to vehicle-treated injured animals. To rule out the possibility that blockade of ADK-L has any effects in non-injured animals, we quantified baseline neural stem cell proliferation in ADKΔneuron mice, which was not altered, whereas baseline neural stem cell proliferation in ADK-Ltg mice was enhanced. Together these findings demonstrate a novel function of ADK-L involved in the regulation of neural stem cell proliferation after TBI.

scholarly journals Neural Stem Cells Therapy to Treat Neurodegenerative Diseases

2021 ◽  
Vol 271 ◽  
pp. 03076
Author(s):  
Weibai Chen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Neural Stem Cells ◽  
Neurodegenerative Diseases ◽  
Cell Transplantation ◽  
Neural Stem Cell ◽  
The Body ◽  
Brain Diseases ◽  
The Brain

Neural stem cells have the ability to proliferation, differentiate and renew, which plays an important role in the growth, maturation and senescence of the human brain. But according to researches, neural stem cells in the brain do not remain active throughout an organism's lifetime. Many neural stem cells become dormant when the brain matures, and may be activated when the body is sick to selectively heal the disease. In recent years, there are many studies on neural stem cells. Joshua[1] and Ting Zhang[2] show that neurodegenerative diseases such as ischemic stroke, Alzheimer's disease and Parkinson's disease can be improved by the transplantation of neural stem cells, however the specific mechanism is not clear. This paper investigates three main questions: Why neural stem cell transplantation is chosen as a treatment? Where does NSCs derive from in clinical transplantation? How does neural stem cell transplantation treat brain diseases? And we also figure out the answers to these three questions. Firstly, transplantation of hypothalamic NSCs can delay the process of aging in the host, and Chemokines and EVs which secreted by neural stem cells can delay aging and defend neurodegenerative diseases. Secondly, the sources of NSCs can be divided into three types. The first is to isolate NSCs from primary tissue and cultivate them in vitro. The second is to produce the required cells by inducing pluripotent stem cells and embryonic stem cells. The third way to get NCS is through transdifferentiation of somatic cells. Thirdly, in brain diseases, transplanted NSCs can migrate from the aggregation site to the site of the disease, reducing damage to the blood-brain barrier, repairing learning and memory abilities that depend on the hippocampus and secreting neurotrophic factors.

scholarly journals Loss of ZC4H2 and RNF220 Inhibits Neural Stem Cell Proliferation and Promotes Neuronal Differentiation

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1600
Author(s):  
Longlong Zhang ◽  
Maosen Ye ◽  
Liang Zhu ◽  
Jingmei Cha ◽  
Chaocui Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Protein Levels ◽  
Ubiquitin E3 Ligase ◽  
Proliferation And Differentiation

The ubiquitin E3 ligase RNF220 and its co-factor ZC4H2 are required for multiple neural developmental processes through different targets, including spinal cord patterning and the development of the cerebellum and the locus coeruleus. Here, we explored the effects of loss of ZC4H2 and RNF220 on the proliferation and differentiation of neural stem cells (NSCs) derived from mouse embryonic cortex. We showed that loss of either ZC4H2 or RNF220 inhibits the proliferation and promotes the differentiation abilities of NSCs in vitro. RNA-Seq profiling revealed 132 and 433 differentially expressed genes in the ZC4H2−/− and RNF220−/− NSCs, compared to wild type (WT) NSCs, respectively. Specifically, Cend1, a key regulator of cell cycle exit and differentiation of neuronal precursors, was found to be upregulated in both ZC4H2−/− and RNF220−/− NSCs at the mRNA and protein levels. The targets of Cend1, such as CyclinD1, Notch1 and Hes1, were downregulated both in ZC4H2−/− and RNF220−/− NSCs, whereas p53 and p21 were elevated. ZC4H2−/− and RNF220−/− NSCs showed G0/G1 phase arrest compared to WT NSCs in cell cycle analysis. These results suggested that ZC4H2 and RNF220 are likely involved in the regulation of neural stem cell proliferation and differentiation through Cend1.

scholarly journals Effects of Radiation Therapy on Neural Stem Cells

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 640 ◽  
Author(s):  
Anna Michaelidesová ◽  
Jana Konířová ◽  
Petr Bartůněk ◽  
Martina Zíková
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Effects ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Brain Radiotherapy ◽  
The Impact ◽  
The Brain

Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.

scholarly journals The Effect of Advanced Motherhood on Newborn Offspring’s Hippocampal Neural Stem Cell Proliferation

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Bo Li ◽  
Ping Duan ◽  
Xuefei Han ◽  
Wenhai Yan ◽  
Ying Xing
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Control Group ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Positive Rate ◽  
Mother Group

Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation.Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis.Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres’ diameter was smaller than that of the control group (P<0.05). The EdU positive rate of the old mother group was lower than that of the control group (P<0.05). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (P<0.05). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (P<0.05).Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group.

scholarly journals Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

2017 ◽  
Author(s):  
Maria Angeles Marques-Torrejon ◽  
Ester Gangoso ◽  
Steven M. Pollard
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Ex Vivo ◽  
Brain Slices ◽  
Genetically Engineered ◽  
Adult Brain ◽  
Host Interactions ◽  
The Brain

AbstractGlioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM tumours can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human). Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring of live cell behaviours. Here we explored whole adult brain coronal organotypic slices as a complementary strategy to remove the experimental bottleneck. Mouse adult brain slices remain viable in a neural stem cell serum-free basal media for several weeks. GSCs can therefore be easily microinjected into specific anatomical sites ex vivo. We demonstrated distinct responses of engrafted GSCs to different microenvironments in the brain. Within the subependymal zone – one of the adult neural stem cell niches – a subset of injected tumour cells could effectively engraft and respond to endothelial niche signals. GSCs transplanted slices were treated with the anti-mitotic drug temozolomide as proof-of-principle of the utility in modelling responses to existing treatments. Thus, engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices provides a convenient experimental model for studies of GSC-host interactions and preclinical testing of candidate therapeutic agents.

Sign in / Sign up

Export Citation Format

Share Document