Epigenetic control of stem cell fate to neurons and glia

Kim, Hyun-Jung; Rosenfeld, Michael G.

doi:10.1007/s12272-010-1001-z

Cited by 28 publications

(21 citation statements)

References 55 publications

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“…Epigenetic mechanisms are often associated with learning and memory [24] and there is increasing evidence that histone modifications are in part responsible for regulating the process of adult hippocampal neurogenesis [25]. Here we demonstrate increased histone H3 acetylation and decreased HDAC activity in the hippocampus of the CMF-treated rats when compared to the saline-treated group.…”

Section: Discussionsupporting

confidence: 50%

Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications

2011

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BackgroundIn this study, we examined the effects of cyclophosphamide, methothrexate, and 5-Fluorouracil (CMF) drug combination on various aspects of learning and memory. We also examined the effects of CMF on cell proliferation and chromatin remodeling as possible underlying mechanisms to explain chemotherapy-associated cognitive dysfunction. Twenty-four adult female Wistar rats were included in the study and had minimitter implantation for continuous activity monitoring two weeks before the chemotherapy regimen was started. Once baseline activity data were collected, rats were randomly assigned to receive either CMF or saline injections given intraperitoneally. Treatments were given once a week for a total of 4 weeks. Two weeks after the last injection, rats were tested in the water maze for spatial learning and memory ability as well as discrimination learning. Bromodeoxyuridine (BrdU) injection was given at 100 mg/Kg intraperitoneally 4 hours prior to euthanasia to determine hippocampal cell proliferation while histone acetylation and histone deacetylase activity was measured to determine CMF effects on chromatin remodeling.ResultsOur data showed learning and memory impairment following CMF administration independent of the drug effects on physical activity. In addition, CMF-treated rats showed decreased hippocampal cell proliferation, associated with increased histone acetylation and decreased histone deacetylase activity.ConclusionsThese results suggest the negative consequences of chemotherapy on brain function and that anti-cancer drugs can adversely affect the self-renewal potential of neural progenitor cells and also chromatin remodeling in the hippocampus. The significance of our findings lie on the possible usefulness of animal models in addressing the clinical phenomenon of 'chemobrain.'

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Section: Discussionsupporting

confidence: 50%

Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications

2011

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“…To evaluate the influence of cell sources and growth factors included in the culture medium, we analyzed the expression of 106 pluripotent and neuronal marker genes (Supporting Information Table S3) [44][45][46][47][48] in diNSC-derived neurospheres established using the various culture conditions shown in Figure 5D, by hierarchical clustering. In this analysis, the MEF-derived neurospheres constituted one group, and the two adult fibroblast-derived neurospheres were clustered separately.…”

Section: Microarray Analysis Of Dinsc-derived Neurospheresmentioning

confidence: 99%

Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency

et al. 2012

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Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation of induced pluripotent stem cells (iPSCs). These NSCs gave rise to both neurons and glial cells even at early passages, while early NSCs derived from clonal embryonic stem cells (ESCs)/ iPSCs differentiated mainly into neurons. Epidermal growth factor-dependent neurosphere cultivation efficiently propagated these gliogenic NSCs and eliminated residual pluripotent cells that could form teratomas in vivo. We concluded that these directly induced NSCs were derived from partially reprogrammed cells, because dissociated ESCs/ iPSCs did not form neurospheres in this culture condition. These NSCs differentiated into both neurons and glial cells in vivo after being transplanted intracranially into mouse striatum. NSCs could also be directly induced from adult human fibroblasts. The direct differentiation of partially reprogrammed cells may be useful for rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis.

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“…The modulation of genome function by the regulation of chromatin structure is now widely appreciated as a central mechanism in the specification of neural cell fates (for reviews, see Kim and Rosenfeld 2010;Lee and Lee 2010;Juliandi et al 2010). DNA methylation and histone modification are recognized as key processes (for a review, see Bernstein et al 2007) and an ever increasing list of histone modifications (for a review, see Bannister and Kouzarides 2011), in part analysed on a genome-wide scale in various cell types, allows associations of modification profiles and transcriptional states to be made.…”

Section: Regulatory Elements In Neuronal Genesmentioning

confidence: 99%

Regulation of gene expression during early neuronal differentiation: evidence for patterns conserved across neuron populations and vertebrate classes

Ernsberger

2012

Cell Tissue Res

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Analysis of transcription factor function during neurogenesis has provided a huge amount of data on the generation and specification of diverse neuron populations in the central and peripheral nervous systems of vertebrates. However, an understanding of the induction of key neuron functions including electrical information processing and synaptic transmission lags seriously behind. Whereas pan-neuronal markers such as neurofilaments, neuron-specific tubulin and RNA-binding proteins have often been included in developmental analysis, the molecular players underlying electrical activity and transmitter release have been neglected in studies addressing gene expression during neuronal induction. Here, I summarize the evidence for a distinct accumulation pattern of mRNAs for synaptic proteins, a pattern that is delayed compared with pan-neuronal gene expression during neurogenesis. The conservation of this pattern across diverse avian and mammalian neuron populations suggests a common mechanism for the regulation of various sets of neuronal genes during initial neuronal differentiation. The co-regulation of genes coding for synaptic proteins from embryonic to postnatal development indicates that the expression of the players required for synaptic transmission shares common regulatory features. For the ion channels involved in neuronal electrical activity, such as voltage-gated sodium channels, the situation is less clear because of the lack of comparative studies early during neurogenesis. Transcription factors have been characterized that regulate the expression of synaptic proteins in vitro and in vivo. They currently do not explain the co-regulation of these genes across different neuron populations. The neuron-restrictive silencing factor NRSF/REST targets a large gene set, but not all of the genes coding for pan-neuronal, synaptic and ion channel proteins. The discrepancy between NRSF/REST loss-of-function and silencer-to-activator-switch studies leaves the full functional implications of this factor open. Together with microRNAs, splicing regulators, chromatin remodellers and an increasing list of transcriptional regulators, the factor is embedded in feedback circuits with the potential to orchestrate neuronal differentiation. The precise regulation of the coordinated expression of proteins underlying key neuronal functions by these circuits during neuronal induction is a major emerging topic.

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Epigenetic control of stem cell fate to neurons and glia

Cited by 28 publications

References 55 publications

Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications

Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications

Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency

Regulation of gene expression during early neuronal differentiation: evidence for patterns conserved across neuron populations and vertebrate classes

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