scholarly journals Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence

Science ◽  
2018 ◽  
Vol 360 (6384) ◽  
pp. 99-102 ◽  
Author(s):  
L. Otsuki ◽  
A. H. Brand
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Cell Activation ◽  
Akt Activation ◽  
Evolutionarily Conserved ◽  
Quiescent Stem Cells

Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in Drosophila are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G0. In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G2 or G0. G2-G0 heterogeneity directs NSC behavior: G2 qNSCs reactivate before G0 qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G2 NSCs to enter quiescence by promoting degradation of Cdc25String and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences trbl transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.

Sevoflurane affects neurogenesis through cell cycle arrest via inhibiting wnt/β-catenin signaling pathway in mouse neural stem cells

Life Sciences ◽  
2018 ◽  
Vol 209 ◽  
pp. 34-42 ◽  
Author(s):  
Shiwen Liu ◽  
Fang Fang ◽  
Ruixue Song ◽  
Xuan Gao ◽  
Ming Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Cycle Arrest

scholarly journals A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Jinsuke Nishino ◽  
Sunjung Kim ◽  
Yuan Zhu ◽  
Hao Zhu ◽  
Sean J Morrison
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Adult Stem Cells ◽  
Rna Binding ◽  
Cell Function ◽  
Temporal Changes ◽  
Evolutionarily Conserved ◽  
Heterochronic Gene ◽  
Heterochronic Genes

Stem cell properties change over time to match the changing growth and regeneration demands of tissues. We showed previously that adult forebrain stem cell function declines during aging because of increased expression of let-7 microRNAs, evolutionarily conserved heterochronic genes that reduce HMGA2 expression. Here we asked whether let-7 targets also regulate changes between fetal and adult stem cells. We found a second let-7 target, the RNA binding protein IMP1, that is expressed by fetal, but not adult, neural stem cells. IMP1 expression was promoted by Wnt signaling and Lin28a expression and opposed by let-7 microRNAs. Imp1-deficient neural stem cells were prematurely depleted in the dorsal telencephalon due to accelerated differentiation, impairing pallial expansion. IMP1 post-transcriptionally inhibited the expression of differentiation-associated genes while promoting the expression of self-renewal genes, including Hmga2. A network of heterochronic gene products including Lin28a, let-7, IMP1, and HMGA2 thus regulates temporal changes in stem cell properties.

scholarly journals Traditional Chinese Medicine Monomers: Novel Strategy for Endogenous Neural Stem Cells Activation After Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Ju Wang ◽  
Jun Hu ◽  
Xuezhu Chen ◽  
Xuejiao Lei ◽  
Hua Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cell Therapy ◽  
Neural Stem Cells ◽  
Signaling Pathway ◽  
Stem Cell Therapy ◽  
Cns Injury ◽  
Endogenous Neural Stem Cells

Stem cell therapy, which has become a potential regenerative medical treatment and a promising approach for treating brain injuries induced by different types of cerebrovascular disease, has various application methods. Activation of endogenous neural stem cells (NSCs) can enable infarcted neuron replacement and promote neural networks’ regeneration without the technical and ethical issues associated with the transplantation of exogenous stem cells. Thus, NSC activation can be a feasible strategy to treat central nervous system (CNS) injury. The potential molecular mechanisms of drug therapy for the activation of endogenous NSCs have gradually been revealed by researchers. Traditional Chinese medicine monomers (TCMs) are active components extracted from Chinese herbs, and some of them have demonstrated the potential to activate proliferation and neurogenesis of NSCs in CNS diseases. Ginsenoside Rg1, astragaloside IV (AST), icariin (ICA), salvianolic acid B (Sal B), resveratrol (RES), curcumin, artesunate (ART), and ginkgolide B (GB) have positive effects on NSCs via different signaling pathways and molecules, such as the Wingless/integrated/β-catenin (Wnt/β-catenin) signaling pathway, the sonic hedgehog (Shh) signaling pathway, brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). This article may provide further motivation for researchers to take advantage of TCMs in studies on CNS injury and stem cell therapy.

Gene Expression Profiling in Quiescent Stem Cells from Normal and Chronic Myeloid Leukaemia Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2962-2962
Author(s):  
Susan M. Graham ◽  
Gerry J. Graham ◽  
Tessa L. Holyoake
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Stem Cell Marker ◽  
Quiescent Cells ◽  
Dividing Cells ◽  
Quiescent Stem Cells

Abstract Earlier studies have shown that Ph+ quiescent cells exist in chronic myeloid leukaemia (CML) (Blood (1999)94:2056) and we have previously shown that these cells are primitive in that they express the stem cell marker CD34. We have also shown that quiescent CML stem cells are insensitive to the effects of imatinib (IM Novartis Pharma) (Blood (2002) 99:319) and may present a possible source for relapse. This quiescent population therefore represents a potentially significant clinical problem and thus studies aimed at developing methods for eradicating this population are timely. In an effort to identify molecular markers of this population that may allow it to be specifically targeted during therapy, we have set out to investigate the transcriptional differences between quiescent and cycling stem cells. To this end, we have used specific stem cell enrichment and sorting protocols. Leukapheresis products from CML patients (N=5) in chronic phase at diagnosis and mobilised peripheral blood from allogeneic donors (N=3), were selected for CD34+ cells. Hoechst 33342 and Pyronin Y were used to discriminate the quiescent (G0) cells identified as Hoechstlo/Pyroninlo from the cycling cells. In combination with propidium iodide for dead cell exclusion we were able to sort 4–9x105 viable, quiescent stem cells and 4–11x106 cycling cells, which were processed for microarrays. Affymetrix gene chips (U133A) were used for the analysis and the data obtained was analysed using GeneSpring. Number of Genes Changed in Each Comparison 3 Fold 4 Fold 5 Fold CML G0 V CML Div 37 21 10 Norm G0 V Norm Div 188 92 47 CML G0 V Norm G0 168 85 49 CML Div V Norm Div 49 27 8 Initial analysis indicates that the greatest differences in gene expression are between the normal quiescent cells (G0) and normal dividing cells (Div) and between the normal quiescent cells and CML quiescent cells. A large percentage of the genes differentially expressed between the quiescent and cycling normal cells encode regulators of the cell cycle confirming the success of the sorting strategy for quiescent and cycling cells A selection of Genes Up-Regulated in Normal Cycling Cells Compared to G0 Gene Fold Up-regulation PCNA 3 CDC2 8 CCNB2 5 CCN1 3.5 CDC20 6 CDC25A 3.5 MCM5 3 In addition, many of the genes identified in our analysis are consistent with other published expression profiles for haemopoietic cells. Curiously, we have identified unanticipated changes in expression of cell cycle genes in the CML quiescent cells, which merit further investigation. We have also identified a number of unexpected genes as being more than 5 fold changed in the quiescent cells compared to dividing cells for both normal and CML samples. Specifically, there is a large cohort of genes preferentially expressed in quiescent normal or CML cells, which encode members of the chemokine family of proteins. Work is ongoing to establish the relevance, if any, of these genes to stem cell quiescence.

scholarly journals Effects of Ginsenoside Rg1 Regulating Wnt/β-Catenin Signaling on Neural Stem Cells to Delay Brain Senescence

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yue Xiang ◽  
Shun-he Wang ◽  
Lu Wang ◽  
Zi-ling Wang ◽  
Hui Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Signaling Pathway ◽  
Brain Aging ◽  
Optical Microscope ◽  
Cell Senescence ◽  
Ginsenoside Rg1 ◽  
Positive Rate ◽  
Culture Identification

This is a study on the relationship between the protective effect of ginsenoside Rg1 on senescent neural stem cells and Wnt-β/catenin signaling pathway. Background. Recent studies have shown that overactivation of the Wnt/β-catenin signaling pathway is closely related to stem cell senescence. Whether Rg1 delays the senescence of NSCs is related to the regulation of this signaling pathway. Methods. The whole brain of Nestin-GFP transgenic newborn rat was extracted, and NSCs were extracted and cultured to P3 generation. The following indicators were detected: (1) NSC culture identification, (2) the effect of LiCl on the proliferation and survival rate of NSCs, (3) the effect of ginsenoside Rg1 on the proliferation and survival of NSCs, (4) the growth of NSCs in each group observed by an optical microscope, (5) the cell cycle of each group detected by flow cytometry, (6) the proliferative ability of each group detected by BrdU, (7) the fluorescence intensity of Nestin and Sox2 of NSCs in each group observed by a fluorescence microscope, (8) the positive rate of senescence staining analyzed by SA-β-Gal staining, (9) the localization of β-catenin in NSCs observed by laser confocal microscopy, and (10) the changes of the Wnt/β-catenin pathway-related proteins in each group detected by Western blotting. Results. LiCl activates the Wnt/β-catenin pathway and promotes mouse neural stem cell senescence. Ginsenoside Rg1 promotes proliferation of neural stem cells and inhibits Wnt/β-catenin pathway activation. Conclusions. LiCl can activate the Wnt/β-catenin signaling pathway of NSCs, and ginsenoside Rg1 can antagonize the senescence of NSCs caused by activation of the Wnt/β-catenin signaling pathway and delay brain aging.

scholarly journals Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hannah S Seidel ◽  
Judith Kimble
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Germline Stem Cells ◽  
Stem Cell Maintenance ◽  
M Phase ◽  
Cell Maintenance

Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells—including germline stem cells—become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions—GLP-1/Notch signaling—becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

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