Balancing self-renewal and differentiation by asymmetric division: Insights from brain tumor suppressors in Drosophila neural stem cells

BioEssays ◽  
2012 ◽  
Vol 34 (4) ◽  
pp. 301-310 ◽  
Author(s):  
Kai Chen Chang ◽  
Cheng Wang ◽  
Hongyan Wang
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Neural Stem Cells ◽  
Tumor Suppressors ◽  
Asymmetric Division ◽  
Self Renewal

scholarly journals Arl2- and Msps-dependent microtubule growth governs asymmetric division

2016 ◽  
Vol 212 (6) ◽  
pp. 661-676 ◽  
Author(s):  
Keng Chen ◽  
Chwee Tat Koe ◽  
Zhanyuan Benny Xing ◽  
Xiaolin Tian ◽  
Fabrizio Rossi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Polarity ◽  
Control Cell ◽  
Asymmetric Division ◽  
New Paradigm ◽  
Self Renewal ◽  
Tubulin Binding ◽  
Microtubule Growth ◽  
Adp Ribosylation Factor

Asymmetric division of neural stem cells is a fundamental strategy to balance their self-renewal and differentiation. It is long thought that microtubules are not essential for cell polarity in asymmetrically dividing Drosophila melanogaster neuroblasts (NBs; neural stem cells). Here, we show that Drosophila ADP ribosylation factor like-2 (Arl2) and Msps, a known microtubule-binding protein, control cell polarity and spindle orientation of NBs. Upon arl2 RNA intereference, Arl2-GDP expression, or arl2 deletions, microtubule abnormalities and asymmetric division defects were observed. Conversely, overactivation of Arl2 leads to microtubule overgrowth and depletion of NBs. Arl2 regulates microtubule growth and asymmetric division through localizing Msps to the centrosomes in NBs. Moreover, Arl2 regulates dynein function and in turn centrosomal localization of D-TACC and Msps. Arl2 physically associates with tubulin cofactors C, D, and E. Arl2 functions together with tubulin-binding cofactor D to control microtubule growth, Msps localization, and NB self-renewal. Therefore, Arl2- and Msps-dependent microtubule growth is a new paradigm regulating asymmetric division of neural stem cells.

scholarly journals STEM-21. INVESTIGATING DOT1L AS AN EPIGENETIC VULNERABILITY IN BRAIN TUMOR STEM CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi238-vi238
Author(s):  
Danielle Bozek ◽  
Graham MacLeod ◽  
Xiaoguang Hao ◽  
Nishani Rajakulendran ◽  
Moloud Ahmadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Brain Tumor ◽  
Neural Stem Cells ◽  
Tumor Growth ◽  
Cell Lines ◽  
Histone Methyltransferase ◽  
Tumor Stem Cells ◽  
Self Renewal ◽  
Brain Tumor Stem Cells

Abstract Glioblastoma (GBM), the most common and aggressive primary adult brain cancer, is thought to be driven by a small subpopulation of brain tumor stem cells (BTSCs). BTSCs exhibit shared properties with normal stem cells such as self-renewal and multilineage differentiation. These stem cell properties have been proposed to underlie GBM tumorigenicity, treatment evasion and contribute to tumor heterogeneity. To investigate the biology underlying the stem cell properties of GBM, we compared gene essentiality profiles for a panel of BTSCs, fetal neural stem cells and non-GBM cell lines using a CRISPR Cas9 knockout library. Interestingly, from these screens, we identified the histone methyltransferase disrupter of telomeric silencing-1-like (DOT1L) as an essential gene for the growth of BTSCs and fetal neural stem cells but not for non-GBM cell lines. DOT1L is the only known histone methyltransferase responsible for histone 3 lysine 79 methylation, an epigenetic mark associated with active gene transcription. The role of this epigenetic regulator in BTSCs was investigated in depth using EPZ-5676, a clinically relevant small molecule inhibitor. Short-term treatment with EPZ-5676 in BTSCs showed minimal effects on cell viability but led to striking morphological changes, increased neuronal and astrocytic differentiation and a reduction in self-renewal. Longer treatment periods with EPZ-5676 led to a decrease in BTSC proliferation and an increase in apoptosis. Furthermore, BTSCs pretreated with EPZ-5676 led to slowed orthotopic tumor growth and improved overall survival in a SCID mouse model. Overall, these findings suggest DOT1L epigenetically regulates GBM stem cell properties and tumor growth. We are further investigating the mechanisms underlying DOT1L regulation of gene expression in BTSCs with the goal of improving the field’s understanding of epigenetics and the therapeutic implications of targeting epigenetic processes in GBM.

The Balance Between Self-Renewal and Differentiation of Human Neural Stem Cells Requires the Amyloid Precursor Protein

2021 ◽  
Author(s):  
Khadijeh Shabani ◽  
Julien Pigeon ◽  
Marwan Benaissa Touil Zariouh ◽  
Tengyuan Liu ◽  
Azadeh Saffarian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Self Renewal ◽  
Human Neural Stem Cells

P50. Role of glioma produced CM1 in the brain tumor tropism of human neural stem cells

2010 ◽  
Vol 80 ◽  
pp. S33-S34
Author(s):  
J. Jeon ◽  
S. Cho ◽  
K. Cho ◽  
Y. Lee ◽  
M. Lee
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells ◽  
Tumor Tropism ◽  
The Brain

scholarly journals Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase–mediated damage of rat fetal neural stem cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeyong Yang ◽  
Jingjing Lv ◽  
Xingxing Li ◽  
Qiong Meng ◽  
Qiling Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Self Renewal

scholarly journals BEND6 is a nuclear antagonist of Notch signaling during self-renewal of neural stem cells

Development ◽  
2013 ◽  
Vol 140 (9) ◽  
pp. 1892-1902 ◽  
Author(s):  
Q. Dai ◽  
C. Andreu-Agullo ◽  
R. Insolera ◽  
L. C. Wong ◽  
S.-H. Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Notch Signaling ◽  
Self Renewal
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