scholarly journals Multiplex mapping of chromatin accessibility and DNA methylation within targeted single molecules identifies epigenetic heterogeneity in neural stem cells and glioblastoma

2013 ◽  
Vol 24 (2) ◽  
pp. 329-339 ◽  
Author(s):  
N. H. Nabilsi ◽  
L. P. Deleyrolle ◽  
R. P. Darst ◽  
A. Riva ◽  
B. A. Reynolds ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Single Molecules ◽  
Chromatin Accessibility

scholarly journals Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain

mSystems ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Sylvie Janssens ◽  
Michael Schotsaert ◽  
Rahul Karnik ◽  
Vinod Balasubramaniam ◽  
Marion Dejosez ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Brain ◽  
Zika Virus ◽  
Brain Disorders ◽  
Epigenetic Changes ◽  
Zikv Infection ◽  
Human Neural Stem Cells ◽  
Neural Genes

Scientific research on human neural stem cells and cerebral organoids has confirmed the congenital neurotropic and neurodestructive nature of the Zika virus. However, the extent to which prenatal ZIKV infection is associated with more subtle brain alterations, such as epigenetic changes, remains ill defined. Here, we address the question of whether ZIKV infection induces DNA methylation changes with the potential to cause brain disorders later in life.

scholarly journals X Chromosome Dosage Modulates Multiple Molecular and Cellular Properties of Mouse Pluripotent Stem Cells Independently of Global DNA Methylation Levels

2018 ◽  
Author(s):  
Juan Song ◽  
Adrian Janiszewski ◽  
Natalie De Geest ◽  
Lotte Vanheer ◽  
Irene Talon ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
Gene Dosage ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Global Dna Methylation ◽  
Open Chromatin ◽  
Mammalian Development

ABSTRACTDuring early mammalian development, the two X-chromosomes in female cells are active. Dosage compensation between XX female and XY male cells is then achieved by X-chromosome inactivation in female cells. Reprogramming female mouse somatic cells into induced pluripotent stem cells (iPSCs) leads to X-chromosome reactivation. The extent to which increased X-chromosome dosage (X-dosage) in female iPSCs leads to differences in the molecular and cellular properties of XX and XY iPSCs is still unclear. We show that chromatin accessibility in mouse iPSCs is modulated by X-dosage. Specific sets of transcriptional regulator motifs are enriched in chromatin with increased accessibility in XX or XY iPSCs. We show that the transcriptome, growth and pluripotency exit are also modulated by X-dosage in iPSCs. To understand the mechanisms by which increased X-dosage modulates the molecular and cellular properties of mouse pluripotent stem cells, we used heterozygous deletions of the X-linked gene Dusp9 in XX embryonic stem cells. We show that X-dosage regulates the transcriptome, open chromatin landscape, growth and pluripotency exit largely independently of global DNA methylation. Our results uncover new insights into X-dosage in pluripotent stem cells, providing principles of how gene dosage modulates the epigenetic and genetic mechanisms regulating cell identity.

scholarly journals Toxicity mechanism of sevoflurane in neural stem cells of rats through DNA methylation

2019 ◽  
Author(s):  
Ka Wang ◽  
Yi Tian ◽  
Yingai Zhang ◽  
Xuying Li ◽  
Xiao Wei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Toxicity Mechanism

scholarly journals Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity

2021 ◽  
Author(s):  
Takashi Kaise ◽  
Masahiro Fukui ◽  
Risa Sueda ◽  
Wenhui Piao ◽  
Mayumi Yamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Genetic Disorder ◽  
Chromatin Accessibility ◽  
Aged Mouse ◽  
Gene Combination ◽  
Age Related ◽  
Nuclear Factors ◽  
Adult Nscs ◽  
Senescence Associated Genes

The regenerative potential of neural stem cells (NSCs) declines during aging, leading to cognitive dysfunctions. This decline involves up-regulation of senescence-associated genes, but inactivation of such genes failed to reverse aging of hippocampal NSCs. Because many genes are up-regulated or down-regulated during aging, manipulation of single genes would be insufficient to reverse aging. Here we searched for a gene combination that can rejuvenate NSCs in the aged mouse brain from nuclear factors differentially expressed between embryonic and adult NSCs and their modulators. We found that a combination of inducing the zinc finger transcription factor gene Plagl2 and inhibiting Dyrk1a, a gene associated with Down syndrome (a genetic disorder known to accelerate aging), rejuvenated aged hippocampal NSCs, which already lost proliferative and neurogenic potential. Such rejuvenated NSCs proliferated and produced new neurons continuously at the level observed in juvenile hippocampi, leading to improved cognition. Epigenome, transcriptome, and live-imaging analyses indicated that this gene combination induces up-regulation of embryo-associated genes and down-regulation of age-associated genes by changing their chromatin accessibility, thereby rejuvenating aged dormant NSCs to function like juvenile active NSCs. Thus, aging of NSCs can be reversed to induce functional neurogenesis continuously, offering a way to treat age-related neurological disorders.

scholarly journals UTX/KDM6A suppresses AP-1 and a gliogenesis program during neural differentiation of human pluripotent stem cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Beisi Xu ◽  
Brett Mulvey ◽  
Muneeb Salie ◽  
Xiaoyang Yang ◽  
Yurika Matsui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Regulation ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Gene Activation ◽  
Histone H3 ◽  
Chromatin Accessibility ◽  
Open Chromatin ◽  
Human Neural Stem Cells

Abstract Background UTX/KDM6A is known to interact and influence multiple different chromatin modifiers to promote an open chromatin environment to facilitate gene activation, but its molecular activities in developmental gene regulation remain unclear. Results We report that in human neural stem cells, UTX binding correlates with both promotion and suppression of gene expression. These activities enable UTX to modulate neural stem cell self-renewal, promote neurogenesis, and suppress gliogenesis. In neural stem cells, UTX has a less influence over histone H3 lysine 27 and lysine 4 methylation but more predominantly affects histone H3 lysine 27 acetylation and chromatin accessibility. Furthermore, UTX suppresses components of AP-1 and, in turn, a gliogenesis program. Conclusions Our findings revealed that UTX coordinates dualistic gene regulation to govern neural stem cell properties and neurogenesis–gliogenesis switch.

scholarly journals Hippocampal neural stem cells are more susceptible to the neurotoxin BMAA than primary neurons: effects on apoptosis, cellular differentiation, neurite outgrowth, and DNA methylation

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Paula Pierozan ◽  
Daiane Cattani ◽  
Oskar Karlsson
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neurodegenerative Disease ◽  
Neurite Outgrowth ◽  
Neural Stem Cell ◽  
Stem Cell Differentiation ◽  
Primary Neurons

Abstract Developmental exposure to the environmental neurotoxin β-N-methylamino-l-alanine (BMAA), a proposed risk factor for neurodegenerative disease, can induce long-term cognitive impairments and neurodegeneration in rats. While rodent studies have demonstrated a low transfer of BMAA to the adult brain, this toxin is capable to cross the placental barrier and accumulate in the fetal brain. Here, we investigated the differential susceptibility of primary neuronal cells and neural stem cells from fetal rat hippocampus to BMAA toxicity. Exposure to 250 µM BMAA induced cell death in neural stem cells through caspase-independent apoptosis, while the proliferation of primary neurons was reduced only at 3 mM BMAA. At the lowest concentrations tested (50 and 100 µM), BMAA disrupted neural stem cell differentiation and impaired neurite development in neural stem cell-derived neurons (e.g., reduced neurite length, the number of processes and branches per cell). BMAA induced no alterations of the neurite outgrowth in primary neurons. This demonstrates that neural stem cells are more susceptible to BMAA exposure than primary neurons. Importantly, the changes induced by BMAA in neural stem cells were mitotically inherited to daughter cells. The persistent nature of the BMAA-induced effects may be related to epigenetic alterations that interfere with the neural stem cell programming, as BMAA exposure reduced the global DNA methylation in the cells. These findings provide mechanistic understanding of how early-life exposure to BMAA may lead to adverse long-term consequences, and potentially predispose for neurodevelopmental disorders or neurodegenerative disease later in life.

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