scholarly journals A Comparative Analysis of Reactive Müller Glia Gene Expression After Light Damage and microRNA-Depleted Müller Glia—Focus on microRNAs

2021 ◽  
Vol 8 ◽  
Author(s):  
Seoyoung Kang ◽  
Daniel Larbi ◽  
Monica Andrade ◽  
Sara Reardon ◽  
Thomas A. Reh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Neuronal Loss ◽  
Muller Glia ◽  
Müller Glia ◽  
Light Damage ◽  
Data Set ◽  
Direct Damage ◽  
Gene Regulatory ◽  
Combined Data

Müller glia (MG) are the predominant glia in the neural retina and become reactive after injury or in disease. microRNAs (miRNAs) are translational repressors that regulate a variety of processes during development and are required for MG function. However, no data is available about the MG miRNAs in reactive gliosis. Therefore, in this study, we aimed to profile miRNAs and mRNAs in reactive MG 7 days after light damage. Light damage was performed for 8 h at 10,000 lux; this leads to rapid neuronal loss and strong MG reactivity. miRNAs were profiled using the Nanostring platform, gene expression analysis was conducted via microarray. We compared the light damage dataset with the dataset of Dicer deleted MG in order to find similarities and differences. We found: (1) The vast majority of MG miRNAs declined in reactive MG 7 days after light damage. (2) Only four miRNAs increased after light damage, which included miR-124. (3) The top 10 genes found upregulated in reactive MG after light damage include Gfap, Serpina3n, Ednrb and Cxcl10. (4) The miRNA decrease in reactive MG 7 days after injury resembles the profile of Dicer-depleted MG after one month. (5) The comparison of both mRNA expression datasets (light damage and Dicer-cKO) showed 1,502 genes were expressed under both conditions, with Maff , Egr2, Gadd45b, and Atf3 as top upregulated candidates. (6) The DIANA-TarBase v.8 miRNA:RNA interaction tool showed that three miRNAs were found to be present in all networks, i.e., after light damage, and in the combined data set; these were miR-125b-5p, let-7b and let-7c. Taken together, results show there is an overlap of gene regulatory events that occur in reactive MG after light damage (direct damage of neurons) and miRNA-depleted MG (Dicer-cKO), two very different paradigms. This suggests that MG miRNAs play an important role in a ubiquitous MG stress response and manipulating these miRNAs could be a first step to attenuate gliosis.

scholarly journals Müller Glia regenerative potential is maintained throughout life despite neurodegeneration and gliosis in the ageing zebrafish retina

2020 ◽  
Author(s):  
Raquel R. Martins ◽  
Mazen Zamzam ◽  
Mariya Moosajee ◽  
Ryan Thummel ◽  
Catarina M. Henriques ◽  
...  
Keyword(s):  
Significant Risk ◽  
Neuronal Loss ◽  
Significant Risk Factor ◽  
Great Promise ◽  
Muller Glia ◽  
Müller Glia ◽  
Light Damage ◽  
Age Related ◽  
Ability To Regenerate ◽  
The Impact

ABSTRACTAgeing is a significant risk factor for degeneration of the retina. Harnessing the regenerative potential of Müller glia cells (MG) in the retina offers great promise for the treatment of blinding conditions. Yet, the impact of ageing on MG regenerative capacity has not yet been considered. Here we show that the zebrafish retina undergoes telomerase-independent age-related neurodegeneration. Yet, this progressive neuronal loss in the ageing retina is insufficient to stimulate the MG regenerative response. Instead, age-related neurodegeneration leads to MG gliosis and loss of vision, similarly to humans. Nevertheless, gliotic MG cells retain Yap expression and the ability to regenerate neurons after acute light damage. Therefore, we identify key differences in the MG response to acute versus chronic damage in the zebrafish retina and show that aged gliotic MG can be stimulated to repair damaged neurons in old age.SUMMARYOur data suggest there are key differences between mechanisms driving regeneration in response to acute damage versus age-related chronic damage. It may be that either the number of cells dying in natural ageing is not enough to stimulate MG to proliferate, or the low number of microglia and respective signals released are not sufficient to trigger MG proliferation. Importantly, we show that gliotic MG cells can be stimulated to repair damaged neurons in old zebrafish retina.

scholarly journals Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5646 ◽  
Author(s):  
Alexandra H. Ranski ◽  
Ashley C. Kramer ◽  
Gregory W. Morgan ◽  
Jennifer L. Perez ◽  
Ryan Thummel
Keyword(s):  
Cell Cycle ◽  
Cellular Localization ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Inner Plexiform Layer ◽  
Muller Glia ◽  
Müller Glia ◽  
Light Damage ◽  
Retinal Regeneration ◽  
Adult Zebrafish

Müller glia in the zebrafish retina respond to retinal damage by re-entering the cell cycle, which generates large numbers of retinal progenitors that ultimately replace the lost neurons. In this study we compared the regenerative outcomes of adult zebrafish exposed to one round of phototoxic treatment with adult zebrafish exposed to six consecutive rounds of phototoxic treatment. We observed that Müller glia continued to re-enter the cell cycle to produce clusters of retinal progenitors in zebrafish exposed to multiple rounds of phototoxic light. Some abnormalities were noted, however. First, we found that retinas exposed to multiple rounds of damage exhibited a greater loss of photoreceptors at 36 hours of light damage than retinas that were exposed to their first round of light damage. In addition, we found that Müller glia appeared to have an increase in the acute gliotic response in retinas exposed to multiple rounds of light treatment. This was evidenced by cellular hypertrophy, changes in GFAP cellular localization, and transient increases in stat3 and gfap expression. Finally, following the sixth round of phototoxic lesion, we observed a significant increase in mis-localized HuC/D-positive amacrine and ganglion cells in the inner plexiform layer and outer retina, and a decreased number of regenerated blue cone photoreceptors. These data add to recent findings that retinal regeneration in adult zebrafish occurs concomitant with Müller glia reactivity and can result in the generation of aberrant neurons. These data are also the first to demonstrate that Müller glia appear to modify their phenotype in response to multiple rounds of phototoxic lesion, exhibiting an increase in acute gliosis while maintaining a remarkable capacity for long-term regeneration of photoreceptors.

scholarly journals A COMPRESSED SENSING BASED APPROACH FOR SUBTYPING OF LEUKEMIA FROM GENE EXPRESSION DATA

2011 ◽  
Vol 09 (05) ◽  
pp. 631-645 ◽  
Author(s):  
WENLONG TANG ◽  
HONGBAO CAO ◽  
JUNBO DUAN ◽  
YU-PING WANG
Keyword(s):  
Gene Expression ◽  
Compressed Sensing ◽  
Gene Expression Analysis ◽  
Expression Data ◽  
Data Set ◽  
New Methods ◽  
Genome Wide ◽  
Different Types ◽  
Genome Wide Data ◽  
Improved Accuracy

With the development of genomic techniques, the demand for new methods that can handle high-throughput genome-wide data effectively is becoming stronger than ever before. Compressed sensing (CS) is an emerging approach in statistics and signal processing. With the CS theory, a signal can be uniquely reconstructed or approximated from its sparse representations, which can therefore better distinguish different types of signals. However, the application of CS approach to genome-wide data analysis has been rarely investigated. We propose a novel CS-based approach for genomic data classification and test its performance in the subtyping of leukemia through gene expression analysis. The detection of subtypes of cancers such as leukemia according to different genetic markups is significant, which holds promise for the individualization of therapies and improvement of treatments. In our work, four statistical features were employed to select significant genes for the classification. With our selected genes out of 7,129 ones, the proposed CS method achieved a classification accuracy of 97.4% when evaluated with the cross validation and 94.3% when evaluated with another independent data set. The robustness of the method to noise was also tested, giving good performance. Therefore, this work demonstrates that the CS method can effectively detect subtypes of leukemia, implying improved accuracy of diagnosis of leukemia.

scholarly journals Gene regulatory networks controlling vertebrate retinal regeneration

Science ◽  
2020 ◽  
Vol 370 (6519) ◽  
pp. eabb8598 ◽  
Author(s):  
Thanh Hoang ◽  
Jie Wang ◽  
Patrick Boyd ◽  
Fang Wang ◽  
Clayton Santiago ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Chromatin Accessibility ◽  
Specific Gene ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Regeneration ◽  
Adult Mice ◽  
Gene Regulatory

Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice after injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.

scholarly journals Neuron subtype-specific effector gene expression in the Motor Ganglion of Ciona

2019 ◽  
Author(s):  
Susanne Gibboney ◽  
Kwantae Kim ◽  
Christopher J. Johnson ◽  
Jameson Orvis ◽  
Paula Martínez-Feduchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Gene Expression Analysis ◽  
Transcriptome Profiling ◽  
Matrix Proteins ◽  
Wide Range ◽  
Specific Effector ◽  
The Central Nervous System ◽  
Differential Gene ◽  
Gene Regulatory

AbstractThe central nervous system of the Ciona larva contains only 177 neurons. The precise regulation of neuron subtype-specific morphogenesis and differentiation observed in during the formation of this minimal connectome offers a unique opportunity to dissect gene regulatory networks underlying chordate neurodevelopment. Here we compare the transcriptomes of two very distinct neuron types in the hindbrain/spinal cord homolog of Ciona, the Motor Ganglion (MG): the Descending decussating neuron (ddN, proposed homolog of Mauthner Cells in vertebrates) and the MG Interneuron 2 (MGIN2). Both types are invariantly represented by a single bilaterally symmetric left/right pair of cells in every larva. Supernumerary ddNs and MGIN2s were generated in synchronized embryos and isolated by fluorescence-activated cell sorting for transcriptome profiling. Differential gene expression analysis revealed ddN- and MGIN2-specific enrichment of a wide range of genes, including many encoding potential “effectors” of subtype-specific morphological and functional traits. More specifically, we identified the upregulation of centrosome-associated, microtubule-stabilizing/bundling proteins and extracellular matrix proteins and axon guidance cues as part of a single intrinsic regulatory program that might underlie the unique polarization of the ddNs, the only descending MG neurons that cross the midline.

scholarly journals Exploiting aberrant mRNA expression in autism for gene discovery and diagnosis

2015 ◽  
Author(s):  
Jinting Guan ◽  
Ence Yang ◽  
Jizhou Yang ◽  
Yong Zeng ◽  
Guoli Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Genetic Heterogeneity ◽  
Gene Expression Analysis ◽  
Autism Spectrum ◽  
Data Set ◽  
Expression Variability ◽  
Aberrant Gene Expression ◽  
Gene Sets ◽  
Aberrant Gene

AbstractAutism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity, which greatly complicates the identification of genetic factors that contribute to the disease. Study designs have mainly focused on group differences between cases and controls. The problem is that, by their nature, group difference-based methods (e.g., differential expression analysis) blur or collapse the heterogeneity within groups. By ignoring genes with variable within-group expression, an important axis of genetic heterogeneity contributing to expression variability among affected individuals has been overlooked. To this end, we develop a new gene expression analysis method—aberrant gene expression analysis, based on the multivariate distance commonly used for outlier detection. Our method detects the discrepancies in gene expression dispersion between groups and identifies genes with significantly different expression variability. Using this new method, we re-visited RNA sequencing data generated from post-mortem brain tissues of 47 ASD and 57 control samples. We identified 54 functional gene sets whose expression dispersion in ASD samples is more pronounced than that in controls, as well as 76 co-expression modules present in controls but absent in ASD samples due to ASD-specific aberrant gene expression. We also exploited aberrantly expressed genes as biomarkers for ASD diagnosis. With a whole blood expression data set, we identified three aberrantly expressed gene sets whose expression levels serve as discriminating variables achieving >70% classification accuracy. In summary, our method represents a novel discovery and diagnostic strategy for ASD. Our findings may help open an expression variability-centered research avenue for other genetically heterogeneous disorders.

scholarly journals Hypoxia tolerance in the Norrin-deficient retina and the chronically hypoxic brain studied at single-cell resolution

2019 ◽  
Vol 116 (18) ◽  
pp. 9103-9114 ◽  
Author(s):  
Jacob S. Heng ◽  
Amir Rattner ◽  
Genevieve L. Stein-O’Brien ◽  
Briana L. Winer ◽  
Bryan W. Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Single Cell ◽  
Rna Sequencing ◽  
Chronic Hypoxia ◽  
Muller Glia ◽  
Müller Glia ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific

The mammalian CNS is capable of tolerating chronic hypoxia, but cell type-specific responses to this stress have not been systematically characterized. In the Norrin KO (NdpKO) mouse, a model of familial exudative vitreoretinopathy (FEVR), developmental hypovascularization of the retina produces chronic hypoxia of inner nuclear-layer (INL) neurons and Muller glia. We used single-cell RNA sequencing, untargeted metabolomics, and metabolite labeling from 13C-glucose to compare WT and NdpKO retinas. In NdpKO retinas, we observe gene expression responses consistent with hypoxia in Muller glia and retinal neurons, and we find a metabolic shift that combines reduced flux through the TCA cycle with increased synthesis of serine, glycine, and glutathione. We also used single-cell RNA sequencing to compare the responses of individual cell types in NdpKO retinas with those in the hypoxic cerebral cortex of mice that were housed for 1 week in a reduced oxygen environment (7.5% oxygen). In the hypoxic cerebral cortex, glial transcriptome responses most closely resemble the response of Muller glia in the NdpKO retina. In both retina and brain, vascular endothelial cells activate a previously dormant tip cell gene expression program, which likely underlies the adaptive neoangiogenic response to chronic hypoxia. These analyses of retina and brain transcriptomes at single-cell resolution reveal both shared and cell type-specific changes in gene expression in response to chronic hypoxia, implying both shared and distinct cell type-specific physiologic responses.

scholarly journals Data set for diet specific differential gene expression analysis in three Spodoptera moths

Data in Brief ◽  
2016 ◽  
Vol 8 ◽  
pp. 448-455 ◽  
Author(s):  
A. Roy ◽  
W.B. Walker ◽  
H. Vogel ◽  
S.K. Kushwaha ◽  
S. Chattington ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Data Set ◽  
Differential Gene Expression Analysis ◽  
Differential Gene

scholarly journals mTORC1-induced retinal progenitor cell overproliferation leads to accelerated mitotic aging and degeneration of descendent Müller glia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Soyeon Lim ◽  
You-Joung Kim ◽  
Sooyeon Park ◽  
Ji-heon Choi ◽  
Younghoon Sung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Tuberous Sclerosis Complex ◽  
Progenitor Cell ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Progenitor ◽  
Mechanistic Target Of Rapamycin ◽  
Glycolytic Gene

Retinal progenitor cells (RPCs) divide in limited numbers to generate the cells comprising vertebrate retina. The molecular mechanism that leads RPC to the division limit, however, remains elusive. Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Müller glia (MG) that degenerate from senescence-associated cell death. We further show the hyperproliferation of Tsc1-deficient RPCs and the degeneration of MG in the mouse retina disappear by concomitant deletion of hypoxia-induced factor 1-a (Hif1a), which induces glycolytic gene expression to support mTORC1-induced RPC proliferation. Collectively, our results suggest that, by having mTORC1 constitutively active, an RPC divides and exhausts mitotic capacity faster than neighboring RPCs, and thus produces retinal cells that degenerate with aging-related changes.

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