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57
A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125
, 2006
"... The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by ex ..."
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The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed ‘‘bivalent domains,’ ’ consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.
Kaiso-deficient mice show resistance to intestinal cancer.
- Mol. Cell. Biol.
, 2006
"... Kaiso is a BTB domain protein that associates with the signaling molecule p120-catenin and binds to the methylated sequence mCGmCG or the nonmethylated sequence CTGCNA to modulate transcription. In Xenopus laevis, xKaiso deficiency leads to embryonic death accompanied by premature gene activation i ..."
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Cited by 22 (0 self)
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Kaiso is a BTB domain protein that associates with the signaling molecule p120-catenin and binds to the methylated sequence mCGmCG or the nonmethylated sequence CTGCNA to modulate transcription. In Xenopus laevis, xKaiso deficiency leads to embryonic death accompanied by premature gene activation in blastulae and upregulation of the xWnt11 gene. Kaiso has also been proposed to play an essential role in mammalian synapsespecific transcription. We disrupted the Kaiso gene in mice to assess its role in mammalian development. Kaiso-null mice were viable and fertile, with no detectable abnormalities of development or gene expression. However, when crossed with tumor-susceptible Apc Min/؉ mice, Kaiso-null mice showed a delayed onset of intestinal tumorigenesis. Kaiso was found to be upregulated in murine intestinal tumors and is expressed in human colon cancers. Our data suggest that Kaiso plays a role in intestinal cancer and may therefore represent a potential target for therapeutic intervention.
Strengths and limitations of the neurosphere culture system
- Mol
, 2006
"... Various methods with slight variations in protocol exist for establishing and expanding neurosphere cultures. Generally, neurospheres are derived from a single-cell suspension of neural stem and progenitor cells isolated from the adult or fetal central nervous system (CNS), but neurosphere cultures ..."
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Various methods with slight variations in protocol exist for establishing and expanding neurosphere cultures. Generally, neurospheres are derived from a single-cell suspension of neural stem and progenitor cells isolated from the adult or fetal central nervous system (CNS), but neurosphere cultures can also be established from ES cells (3). The starting pop-ulation of cells is usually plated as a single-cell suspension on uncoated plastic in a N2 and/or
Proliferating versus differentiating stem and cancer cells exhibit distinct midbody-release behaviour
"... The central portion of the midbody, a cytoplasmic bridge between nascent daughter cells at the end of cell division, has generally been thought to be retained by one of the daughter cells, but has, recently, also been shown to be released into the extracellular space. The significance of midbody-ret ..."
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Cited by 10 (0 self)
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The central portion of the midbody, a cytoplasmic bridge between nascent daughter cells at the end of cell division, has generally been thought to be retained by one of the daughter cells, but has, recently, also been shown to be released into the extracellular space. The significance of midbody-retention versus-release is unknown. Here we show, by quantitatively analysing midbody-fate in various cell lines under different growth conditions, that the extent of midbody-release is significantly greater in stem cells than cancer-derived cells. Induction of cell differentiation is accompanied by an increase in midbody-release. Knockdown of the endosomal sorting complex required for transport family members, Alix and tumour-suppressor gene 101, or of their interaction partner, centrosomal protein 55, impairs midbody-release, suggesting mechanistic similarities to abscission. Cells with such impaired midbody-release exhibit enhanced responsiveness to a differentiation stimulus. Taken together, midbody-release emerges as a characteristic feature of cells capable of differentiation.
Radial glia and neural stem cells
- Cell Tissue Res
, 2008
"... All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately. ..."
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Cited by 2 (0 self)
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All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately.
101 PUBLICATIONS 7,316 CITATIONS SEE PROFILE
, 2009
"... All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately. ..."
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All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately.
Bilirubin as a Determinant for Altered Neurogenesis,
, 2009
"... ABSTRACT: Elevated levels of serum unconju-gated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy ..."
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ABSTRACT: Elevated levels of serum unconju-gated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undif-ferentiated neural precursor cells and their fate deci-sions, as well as the development of hippocampal neu-rons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of prolifer-ating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunc-tion in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differen-tiation, development, and plasticity may compromise the performance of the brain in later life. ' 2009 Wiley Periodi-
D E V E
"... One candidate treatment for Parkinson’s disease is cell replacement therapy. Embryonic stem cells have been found to differentiate into dopaminergic (DA) neurons capable of integrating into the adult brain in vivo, and incorporating into functional circuits in animal ..."
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One candidate treatment for Parkinson’s disease is cell replacement therapy. Embryonic stem cells have been found to differentiate into dopaminergic (DA) neurons capable of integrating into the adult brain in vivo, and incorporating into functional circuits in animal
D E V E
"... One candidate treatment for Parkinson’s disease is cell replacement therapy. Embryonic stem cells have been found to differentiate into dopaminergic (DA) neurons capable of integrating into the adult brain in vivo, and incorporating into functional circuits in animal ..."
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One candidate treatment for Parkinson’s disease is cell replacement therapy. Embryonic stem cells have been found to differentiate into dopaminergic (DA) neurons capable of integrating into the adult brain in vivo, and incorporating into functional circuits in animal
Progenitor Cells by Gene Knockdown Approach
"... This paper was published in DNA and Cell Biology and is made available as an electronic reprint (preprint) with permission of Mary Ann Liebert, Inc. The paper can be found at the following official DOI: ..."
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This paper was published in DNA and Cell Biology and is made available as an electronic reprint (preprint) with permission of Mary Ann Liebert, Inc. The paper can be found at the following official DOI:
