The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Johnny Huard - One of the best experts on this subject based on the ideXlab platform.
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study of muscle Cell Dedifferentiation after skeletal muscle injury of mice with a cre lox system
PLOS ONE, 2011Co-Authors: Xiaodong Mu, Hairong Peng, Johnny Huard, Yong LiAbstract:Background Dedifferentiation of muscle Cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle Cell Dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated Cell populations of myotubes and non-fused mononuclear Cells, including stem Cells that can coexist within the population of Cells being studied. Methodology/Principal Findings In the current study, we created a Cre/Lox-β-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear Cells based on the activation of the marker gene, β-galactosidase. By using this system in an adult mouse model, we found that β-galactosidase positive mononuclear Cells were generated from β-galactosidase positive multinuclear myofibers upon muscle injury. We also demonstrated that these mononuclear Cells can develop into a variety of different muscle Cell lineages, i.e., myoblasts, satellite Cells, and muscle derived stem Cells. Conclusions/Significance These novel findings demonstrated, for the first time, that Cellular Dedifferentiation of skeletal muscle Cells actually occurs in mammalian skeletal muscle following traumatic injury in vivo.
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study of muscle Cell Dedifferentiation after skeletal muscle injury of mice with a cre lox system
PLOS ONE, 2011Co-Authors: Hairong Peng, Johnny Huard, Haiying PanAbstract:Background Dedifferentiation of muscle Cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle Cell Dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated Cell populations of myotubes and non-fused mononuclear Cells, including stem Cells that can coexist within the population of Cells being studied.
P Obrist - One of the best experts on this subject based on the ideXlab platform.
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the transcription factor zeb1 δef1 promotes tumour Cell Dedifferentiation by repressing master regulators of epithelial polarity
Oncogene, 2007Co-Authors: Kirsten Aigner, Brigitta Dampier, L Descovich, Mario Mikula, Aneesa Sultan, Martin Schreiber, Wolfgang Mikulits, Thomas Brabletz, Dennis Strand, P ObristAbstract:The transcription factor ZEB1 ( δ EF1) promotes tumour Cell Dedifferentiation by repressing master regulators of epithelial polarity
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The transcription factor ZEB1 (δEF1) promotes tumour Cell Dedifferentiation by repressing master regulators of epithelial polarity
Oncogene, 2007Co-Authors: Kirsten Aigner, Brigitta Dampier, L Descovich, Mario Mikula, Aneesa Sultan, Martin Schreiber, Wolfgang Mikulits, Thomas Brabletz, Dennis Strand, P ObristAbstract:Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumourigenesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer Cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and Cell–Cell adhesion, including the Cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo , and strongly repressed promotor activities in reporter assays. ZEB1 downregulation in undifferentiated cancer Cells by RNA interference was sufficient to upregulate expression of these Cell polarity genes on the RNA and protein level, to re-establish epithelial features and to impair Cell motility in vitro . In human colorectal cancer, ZEB1 expression was limited to the tumour–host interface and was accompanied by loss of interCellular adhesion and tumour Cell invasion. In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer Cell Dedifferentiation. Our data show that ZEB1 represents a key player in pathologic EMTs associated with tumour progression.
José-alain Sahel - One of the best experts on this subject based on the ideXlab platform.
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Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium Cell Dedifferentiation
Journal of Neuroinflammation, 2018Co-Authors: Sara Touhami, Thibaud Mathis, Fanny Beguier, Sacha Reichman, Sébastien Augustin, Hugo Charles-messance, Lucile Vignaud, Emeline F. Nandrot, Valérie Forster, José-alain SahelAbstract:Background The retinal pigment epithelium (RPE) is a monolayer of pigmented Cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE Cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE Cell morphology and key functions in vitro. Methods Primary porcine RPE Cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE Cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed. Results Chronic (10 days) exposure of primary RPE Cells to TNFα increases RPE Cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor β inhibition. Conclusions Our results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE Cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.
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Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium Cell Dedifferentiation.
Journal of Neuroinflammation, 2018Co-Authors: Sara Touhami, Thibaud Mathis, Fanny Beguier, Sacha Reichman, Sébastien Augustin, Hugo Charles-messance, Lucile Vignaud, Emeline F. Nandrot, Valérie Forster, José-alain SahelAbstract:The retinal pigment epithelium (RPE) is a monolayer of pigmented Cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE Cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE Cell morphology and key functions in vitro. Primary porcine RPE Cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE Cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed. Chronic (10 days) exposure of primary RPE Cells to TNFα increases RPE Cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor β inhibition. Our results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE Cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.
Kirsten Aigner - One of the best experts on this subject based on the ideXlab platform.
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the transcription factor zeb1 δef1 promotes tumour Cell Dedifferentiation by repressing master regulators of epithelial polarity
Oncogene, 2007Co-Authors: Kirsten Aigner, Brigitta Dampier, L Descovich, Mario Mikula, Aneesa Sultan, Martin Schreiber, Wolfgang Mikulits, Thomas Brabletz, Dennis Strand, P ObristAbstract:The transcription factor ZEB1 ( δ EF1) promotes tumour Cell Dedifferentiation by repressing master regulators of epithelial polarity
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The transcription factor ZEB1 (δEF1) promotes tumour Cell Dedifferentiation by repressing master regulators of epithelial polarity
Oncogene, 2007Co-Authors: Kirsten Aigner, Brigitta Dampier, L Descovich, Mario Mikula, Aneesa Sultan, Martin Schreiber, Wolfgang Mikulits, Thomas Brabletz, Dennis Strand, P ObristAbstract:Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumourigenesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer Cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and Cell–Cell adhesion, including the Cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo , and strongly repressed promotor activities in reporter assays. ZEB1 downregulation in undifferentiated cancer Cells by RNA interference was sufficient to upregulate expression of these Cell polarity genes on the RNA and protein level, to re-establish epithelial features and to impair Cell motility in vitro . In human colorectal cancer, ZEB1 expression was limited to the tumour–host interface and was accompanied by loss of interCellular adhesion and tumour Cell invasion. In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer Cell Dedifferentiation. Our data show that ZEB1 represents a key player in pathologic EMTs associated with tumour progression.
Xiaodong Mu - One of the best experts on this subject based on the ideXlab platform.
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study of muscle Cell Dedifferentiation after skeletal muscle injury of mice with a cre lox system
PLOS ONE, 2011Co-Authors: Xiaodong Mu, Hairong Peng, Johnny Huard, Yong LiAbstract:Background Dedifferentiation of muscle Cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle Cell Dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated Cell populations of myotubes and non-fused mononuclear Cells, including stem Cells that can coexist within the population of Cells being studied. Methodology/Principal Findings In the current study, we created a Cre/Lox-β-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear Cells based on the activation of the marker gene, β-galactosidase. By using this system in an adult mouse model, we found that β-galactosidase positive mononuclear Cells were generated from β-galactosidase positive multinuclear myofibers upon muscle injury. We also demonstrated that these mononuclear Cells can develop into a variety of different muscle Cell lineages, i.e., myoblasts, satellite Cells, and muscle derived stem Cells. Conclusions/Significance These novel findings demonstrated, for the first time, that Cellular Dedifferentiation of skeletal muscle Cells actually occurs in mammalian skeletal muscle following traumatic injury in vivo.