The Experts below are selected from a list of 28728 Experts worldwide ranked by ideXlab platform
Colin J Barnstable - One of the best experts on this subject based on the ideXlab platform.
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Pluripotent Stem Cells as Models of Retina Development
Molecular Neurobiology, 2019Co-Authors: Colin J BarnstableAbstract:The ability of pluripotent stem cells (PSCs) to differentiate into Retinal tissue has led to many attempts to direct this process to yield specific Retinal cell types. The ability to do so would greatly impact both the study of normal Retina Development in model systems that can be precisely controlled and the generation of a homogeneous population of cells optimized for transplantation in cell replacement therapy. Thus far, many reviews have focused on the translational potential of PSC Retinal studies. Here, we focus on the former by summarizing the advances and reflecting on the current limitations to using in vitro differentiation of PSCs into Retinal cells and organoids to model in vivo Retinal Development, with a specific emphasis on photoreceptors. We discuss the versatility of PSC Retinal differentiation systems in investigating specific Developmental time points that are difficult to assess with classic Developmental model systems as well as the potential for efficient screening of factors involved in regulating photoreceptor differentiation. PSCs can be used in conjunction with existing model systems to contribute to the understanding of Retina and photoreceptor Development, which in turn can enhance the success of using stem cells in translational studies.
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Developmentally regulated linker histone h1c promotes heterochromatin condensation and mediates structural integrity of rod photoreceptors in mouse Retina
Journal of Biological Chemistry, 2013Co-Authors: Evgenya Y Popova, Yuhong Fan, Sergei A. Grigoryev, Samuel S Zhang, Colin J BarnstableAbstract:Mature rod photoreceptor cells contain very small nuclei with tightly condensed heterochromatin. We observed that during mouse rod maturation, the nucleosomal repeat length increases from 190 bp at postnatal day 1 to 206 bp in the adult Retina. At the same time, the total level of linker histone H1 increased reaching the ratio of 1.3 molecules of total H1 per nucleosome, mostly via a dramatic increase in H1c. Genetic elimination of the histone H1c gene is functionally compensated by other histone variants. However, Retinas in H1c/H1e/H10 triple knock-outs have photoreceptors with bigger nuclei, decreased heterochromatin area, and notable morphological changes suggesting that the process of chromatin condensation and rod cell structural integrity are partly impaired. In triple knock-outs, nuclear chromatin exposed several epigenetic histone modification marks masked in the wild type chromatin. Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during Development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus. During Retina Development, the H1c gene and its promoter acquired epigenetic patterns typical of rod-specific genes. Our data suggest that histone H1c gene expression is Developmentally up-regulated to promote facultative heterochromatin in mature rod photoreceptors.
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a biphasic pattern of gene expression during mouse Retina Development
BMC Developmental Biology, 2006Co-Authors: Samuel Shaomin Zhang, Colin J Barnstable, M G Liu, Hongyu Zhao, Marcelo B SoaresAbstract:Background Between embryonic day 12 and postnatal day 21, six major neuronal and one glia cell type are generated from multipotential progenitors in a characteristic sequence during mouse Retina Development. We investigated expression patterns of Retina transcripts during the major embryonic and postnatal Developmental stages to provide a systematic view of normal mouse Retina Development,
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stat3 mediated signaling in the determination of rod photoreceptor cell fate in mouse Retina
Investigative Ophthalmology & Visual Science, 2004Co-Authors: Samuel Shaomin Zhang, Jiye Wei, Hua Qin, Lixin Zhang, Bing Xie, Pei Hui, Albert B Deisseroth, Colin J BarnstableAbstract:Purpose The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the Development of rod photoreceptors in the mouse Retina. Methods Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted Retinas were harvested at distinct time points and processed for immunohistochemistry. Results Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal Development of rods in Retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod Development by CNTF. Conclusions These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor Development during mouse Retina Development.
Yvan Arsenijevic - One of the best experts on this subject based on the ideXlab platform.
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Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation
Molecular Therapy, 2017Co-Authors: Sarah Decembrini, Catherine Martin, Florian Sennlaub, Sylvain Chemtob, Martin Biel, Marijana Samardzija, Alexandre Moulin, Francine Behar-cohen, Yvan ArsenijevicAbstract:The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the Retina, cone tracing during Development would be an important added value. To that aim, the Chrnb4-EGFP mouse line was characterized throughout retinogenesis. It revealed a sub-population of early Retinal progenitors expressing the reporter gene that is progressively restricted to mature cones during Retina Development. The presence of the native CHRNB4 protein was confirmed in EGFP-positive cells, and it presents a similar pattern in the human Retina. Sub-Retinal transplantations of distinct subpopulations of Chrnb4-EGFP-expressing cells revealed the embryonic day 15.5 high-EGFP population the most efficient cells to interact with host Retinas to provoke the appearance of EGFP-positive cones in the photoreceptor layer. Importantly, transplantations into the DsRed Retinas revealed material exchanges between donor and host Retinas, as >80% of transplanted EGFP-positive cones also were DsRed positive. Whether this cell material fusion is of significant therapeutic advantage requires further thorough investigations. The Chrnb4-EGFP mouse line definitely opens new research perspectives in cone genesis and Retina repair.
Sarah Decembrini - One of the best experts on this subject based on the ideXlab platform.
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Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation
Molecular Therapy, 2017Co-Authors: Sarah Decembrini, Catherine Martin, Florian Sennlaub, Sylvain Chemtob, Martin Biel, Marijana Samardzija, Alexandre Moulin, Francine Behar-cohen, Yvan ArsenijevicAbstract:The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the Retina, cone tracing during Development would be an important added value. To that aim, the Chrnb4-EGFP mouse line was characterized throughout retinogenesis. It revealed a sub-population of early Retinal progenitors expressing the reporter gene that is progressively restricted to mature cones during Retina Development. The presence of the native CHRNB4 protein was confirmed in EGFP-positive cells, and it presents a similar pattern in the human Retina. Sub-Retinal transplantations of distinct subpopulations of Chrnb4-EGFP-expressing cells revealed the embryonic day 15.5 high-EGFP population the most efficient cells to interact with host Retinas to provoke the appearance of EGFP-positive cones in the photoreceptor layer. Importantly, transplantations into the DsRed Retinas revealed material exchanges between donor and host Retinas, as >80% of transplanted EGFP-positive cones also were DsRed positive. Whether this cell material fusion is of significant therapeutic advantage requires further thorough investigations. The Chrnb4-EGFP mouse line definitely opens new research perspectives in cone genesis and Retina repair.
Samuel Shaomin Zhang - One of the best experts on this subject based on the ideXlab platform.
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a biphasic pattern of gene expression during mouse Retina Development
BMC Developmental Biology, 2006Co-Authors: Samuel Shaomin Zhang, Colin J Barnstable, M G Liu, Hongyu Zhao, Marcelo B SoaresAbstract:Background Between embryonic day 12 and postnatal day 21, six major neuronal and one glia cell type are generated from multipotential progenitors in a characteristic sequence during mouse Retina Development. We investigated expression patterns of Retina transcripts during the major embryonic and postnatal Developmental stages to provide a systematic view of normal mouse Retina Development,
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stat3 mediated signaling in the determination of rod photoreceptor cell fate in mouse Retina
Investigative Ophthalmology & Visual Science, 2004Co-Authors: Samuel Shaomin Zhang, Jiye Wei, Hua Qin, Lixin Zhang, Bing Xie, Pei Hui, Albert B Deisseroth, Colin J BarnstableAbstract:Purpose The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the Development of rod photoreceptors in the mouse Retina. Methods Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted Retinas were harvested at distinct time points and processed for immunohistochemistry. Results Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal Development of rods in Retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod Development by CNTF. Conclusions These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor Development during mouse Retina Development.
Cornelia A. Deeg - One of the best experts on this subject based on the ideXlab platform.
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Article Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
2016Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. DeegAbstract:Abstract: Retinal pigment epithelium (RPE) builds the outer blood-Retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and Retina Development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and Retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic Retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not Retina, in ERU. Moreover, peripherin 2 is clearly detectabl
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Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
International journal of molecular sciences, 2015Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. DeegAbstract:Retinal pigment epithelium (RPE) builds the outer blood-Retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and Retina Development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and Retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic Retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not Retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in uveitis.