Phenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells

Suter, David M.; Preynat‐Seauve, Olivier; Tirefort, Diderik; Féki, Anis; Krause, Karl‐Heinz

doi:10.1111/j.1582-4934.2008.00660.x

Cited by 19 publications

(25 citation statements)

References 20 publications

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“…Heterogeneity between colonies was confirmed using two other neural progenitor cells markers, Pax‐6 and Sox‐1 (data not shown). Heterogeneity between colonies for neural commitment was confirmed using a genetically modified ESC line expressing the green fluorescent protein (GFP) under the control of the early neural‐specific promoter Tα1 [9]. ESC‐Tα1‐GFP submitted to neural differentiation in the same experimental colonies generated multiple colonies (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cellular diversity within embryonic stem cells: pluripotent clonal sublines show distinct differentiation potential

Martinez

Béna

Gimelli

et al. 2012

J Cellular Molecular Medi

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Embryonic stem cells (ESC), derived from the early inner cell mass (ICM), are constituted of theoretically homogeneous pluripotent cells. Our study was designed to test this concept using experimental approaches that allowed characterization of progenies derived from single parental mouse ESC. Flow cytometry analysis showed that a fraction of ESC submitted to neural differentiation generates progenies that escape the desired phenotype. Live imaging of individual cells demonstrated significant variations in the capacity of parental ESC to generate neurons, raising the possibility of clonal diversity among ESC. To further substantiate this hypothesis, clonal sublines from ESC were generated by limit dilution. Transcriptome analysis of undifferentiated sublines showed marked differences in gene expression despite the fact that all clones expressed pluripotency markers. Sublines showed distinct differentiation potential, both in phenotypic differentiation assays and with respect to gene expression in embryoid bodies. Clones generated from another ESC line also showed individualities in their differentiation potential, demonstrating the wider applicability of these findings. Taken together, our observations demonstrate that pluripotent ESC consist of individual cell types with distinct differentiation potentials. These findings identify novel elements for the biological understanding of ESC and provide new tools with a major potential for their future in vitro and in vivo use.

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Section: Resultsmentioning

confidence: 99%

Cellular diversity within embryonic stem cells: pluripotent clonal sublines show distinct differentiation potential

Martinez

Béna

Gimelli

et al. 2012

J Cellular Molecular Medi

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“…They were differentiated into neutrophil-like cells by dimethylsulphoxide (DMSO; 1.26%) 5 days before use. Astrocytes were derived from human embryonic stem cells as described [17] .…”

Section: Cell Culturementioning

confidence: 99%

NOX4 Expression in Human Microglia Leads to Constitutive Generation of Reactive Oxygen Species and to Constitutive IL-6 Expression

Bedard

Sorce

et al. 2009

J Innate Immun

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pression of the microglia-typical genes MHCII, CD68 and CD11b, nor did it affect the expression of iNOS, VEGF or TGF-␤ . However, there was a marked decrease in IL-6 mRNA. Taken together, we demonstrate a constitutive NOX4-dependent ROS generation in a microglial cell line which leads to expression of IL-6 mRNA. The possibility that microglia could switch from tightly regulated NOX2-dependent ROS generation to constitutive NOX4-dependent ROS generation is of interest for the understanding of the role of microglia in maintaining the balance between neuroprotection and neuroinflammatory damage.

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“…The influence of Phenazopyridine on neuronal differentiation of ES cells was discovered in a screening of a FDA-approved drug library looking at the induction of neuronal specific T 1 -tubulin promoter [49]. The authors suggest that Phenazopyridine might act via metabotropic glutamate receptor 5 (mGluR5) as its structure is similar to the non-competitive mGluR5 antagonists SIB-1757 and SIB-1893 [49]. The authors suggest that Phenazopyridine might act via metabotropic glutamate receptor 5 (mGluR5) as its structure is similar to the non-competitive mGluR5 antagonists SIB-1757 and SIB-1893 [49].…”

Section: Differentiationmentioning

confidence: 99%

Small Molecules in Stem Cell Research

Schmöle¹,

Hübner²,

Beller³

et al. 2013

Current Pharmaceutical Biotechnology

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Stem cells possess great promise as therapeutic tools for neurological disorders such as neurodegenerative diseases (Parkinson's disease and Huntington's disease), cerebrovascular diseases (stroke), neurotraumata (spinal cord injury) and demyelinating diseases (multiple sclerosis). This aspiration is based on the cells` ability to maintain a status of self-renewal and to differentiate into the various cell types of an organism. The use of the cells ranges from in vitro to in vivo studies in animal models, ending with clinical applications in humans. The self-renewal and commitment of stem/progenitor cells to differentiate and mature involves complex events leading to the generation of different phenotypes via distinctive developmental programs. Small molecules provide a tool with which to influence these regulatory changes in a controlled manner and to help understand the underlying mechanisms. Furthermore, substantial progress in generating induced pluripotent stem cells has been made using small molecules to replace reprogramming factors and enhance the reprogramming efficiency and kinetics, thus generating cells more compatible with the requirements for cell replacement therapies. In this review we will present the recent progress on the use of small molecules in embryonic and induced pluripotent stem cell research. In the final section we will give a short summary of the clinical approaches using these cells.

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Phenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells

Abstract: IntroductionEmbryonic stem (ES)

Cited by 19 publications

References 20 publications

Cellular diversity within embryonic stem cells: pluripotent clonal sublines show distinct differentiation potential

Cellular diversity within embryonic stem cells: pluripotent clonal sublines show distinct differentiation potential

NOX4 Expression in Human Microglia Leads to Constitutive Generation of Reactive Oxygen Species and to Constitutive IL-6 Expression

Small Molecules in Stem Cell Research

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