scholarly journals Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
You Ning ◽  
Jian-Hua Huang ◽  
Shi-Jin Xia ◽  
Qin Bian ◽  
Yang Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Dna Microarray ◽  
Specific Gene ◽  
Specific Marker ◽  
Dependent Manner ◽  
Adult Neural Stem Cells ◽  
Medicine Research ◽  
Novel Treatments

Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit ofPsoralea corylifolia L., on NSC behaviors and the underlying mechanisms. The self-renewal and proliferation of NSC were examined. We detected neuron- and/or astrocyte-specific markers using immunofluorescence and Western blotting, which could evaluate NSC differentiation. Psoralen treatment significantly inhibited neurosphere formation in a dose-dependent manner. Psoralen treatment increased the expression of the astrocyte-specific marker but decreased neuron-specific marker expression. These results suggested that Psoralen was a differentiation inducer in astrocyte. Differential gene expression following Psoralen treatment was screened using DNA microarray and confirmed by quantitative real-time PCR. Our microarray study demonstrated that Psoralen could effectively regulate the specific gene expression profile of NSC. The genes involved in the classification of cellular differentiation, proliferation, and metabolism, the transcription factors belonging to Ets family, and the hedgehog pathway may be closely related to the regulation.

scholarly journals Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
You Ning ◽  
Jianhua Huang ◽  
Bill Kalionis ◽  
Qin Bian ◽  
Jingcheng Dong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Oleanolic Acid ◽  
Maximum Effect ◽  
Regulatory Sequences ◽  
Specific Marker ◽  
Dependent Manner ◽  
Protein Levels ◽  
Pentacyclic Triterpenoid

Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage. NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders. Thus far, few drugs have been developed for controlling NSC functions. Here, the effect as well as mechanism of oleanolic acid (OA), a pentacyclic triterpenoid, on NSC function was investigated. We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM. OA also reduced 5-ethynyl-2′-deoxyuridine (EdU) incorporation into NSCs, which was indicative of inhibited NSC proliferation. Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-βIII (TuJ1) and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. Immunofluorescence analysis showed OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells. Using DNA microarray analysis, 183 genes were differentially regulated by OA. Through transcription factor binding site analyses of the upstream regulatory sequences of these genes, 87 genes were predicted to share a common motif for Nkx-2.5 binding. Finally, small interfering RNA (siRNA) methodology was used to silence Nkx-2.5 expression and found silence of Nkx-2.5 alone did not change the expression of TuJ-1 and the percentage of TuJ-1-positive cells. But in combination of OA treatment and silence of Nkx-2.5, most effects of OA on NSCs were abolished. These results indicated that OA is an effective inducer for NSCs differentiation into neurons at least partially by Nkx-2.5-dependent mechanism.

Catalog of gene expression in adult neural stem cells and their in vivo microenvironment

2006 ◽  
Vol 312 (10) ◽  
pp. 1798-1812 ◽  
Author(s):  
Cecilia Williams ◽  
Valtteri Wirta ◽  
Konstantinos Meletis ◽  
Lilian Wikström ◽  
Leif Carlsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Adult Neural Stem Cells

Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2367-2382 ◽  
Author(s):  
M.V. Zappone ◽  
R. Galli ◽  
R. Catena ◽  
N. Meani ◽  
S. De Biasi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Stem Cells ◽  
Transcription Factors ◽  
Neural Stem Cells ◽  
Ventricular Zone ◽  
Specific Gene ◽  
Regulatory Sequences ◽  
Enhancer Element ◽  
Dorsal Telencephalon

Sox2 is one of the earliest known transcription factors expressed in the developing neural tube. Although it is expressed throughout the early neuroepithelium, we show that its later expression must depend on the activity of more than one regionally restricted enhancer element. Thus, by using transgenic assays and by homologous recombination-mediated deletion, we identify a region upstream of Sox2 (−5.7 to −3.3 kb) which can not only drive expression of a (beta)-geo transgene to the developing dorsal telencephalon, but which is required to do so in the context of the endogenous gene. The critical enhancer can be further delimited to an 800 bp fragment of DNA surrounding a nuclease hypersensitive site within this region, as this is sufficient to confer telencephalic expression to a 3.3 kb fragment including the Sox2 promoter, which is otherwise inactive in the CNS. Expression of the 5.7 kb Sox2(beta)-geo transgene localizes to the neural plate and later to the telencephalic ventricular zone. We show, by in vitro clonogenic assays, that transgene-expressing (and thus G418-resistant) ventricular zone cells include cells displaying functional properties of stem cells, i.e. self-renewal and multipotentiality. We further show that the majority of telencephalic stem cells express the transgene, and this expression is largely maintained over two months in culture (more than 40 cell divisions) in the absence of G418 selective pressure. In contrast, stem cells grown in parallel from the spinal cord never express the transgene, and die in G418. Expression of endogenous telencephalic genes was similarly observed in long-term cultures derived from the dorsal telencephalon, but not in spinal cord-derived cultures. Thus, neural stem cells of the midgestation embryo are endowed with region-specific gene expression (at least with respect to some networks of transcription factors, such as that driving telencephalic expression of the Sox2 transgene), which can be inherited through multiple divisions outside the embryonic environment.

Quantitative analysis of gene expression in living adult neural stem cells by gene trapping

2005 ◽  
Vol 2 (5) ◽  
pp. 363-370 ◽  
Author(s):  
John R Scheel ◽  
Jasodhara Ray ◽  
Fred H Gage ◽  
Carrolee Barlow
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Quantitative Analysis ◽  
Neural Stem Cells ◽  
Adult Neural Stem Cells ◽  
Gene Trapping ◽  
Living Adult
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