RNA-Seq reveals differential expression profiles and functional annotation of genes involved in retinal degeneration in Pde6c mutant Danio rerio

Saddala, Madhu Sudhana; Lennikov, Anton; Bouras, Adam; Hu, Huang

doi:10.1186/s12864-020-6550-z

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…Pathway enrichment was performed from both KEGG and REACTOME databases. The top 10 pathways mutually identified in both databases and ranked by their p -value (Saddala et al, 2020 ) are shown in Figure 3 . Electron transport chains, citric acid cycle, nicotinamide scavenging, Alzheimer's disease and Huntington’s disease pathways were upregulated and identified from both the databases.…”

Section: Resultsmentioning

confidence: 99%

Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19

Aishwarya

Gunasekaran

Margret³

2020

Journal of Biomolecular Structure and Dynamics

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The coronavirus disease, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health crisis that is being endured with an increased alarm of transmission each day. Though the pandemic has activated innumerable research attention to decipher an antidote, fundamental understanding of the molecular mechanisms is necessary to halt the disease progression. The study focused on comparison of the COVID-19 infected lung tissue gene expression datasets-GSE155241 and GSE150316 with the GEO2R-limma package. The significant up-and downregulated genes were annotated. Further evaluation of the enriched pathways, transcription factors, kinases, noncoding RNAs and drug perturbations revealed the significant molecular mechanisms of the host response. The results revealed a surge in mitochondrial respiration, cytokines, neurodegenerative mechanisms and deprived oxygen, iron, copper, and glucose transport. Hijack of ubiquitination by SARS-CoV-2, hox gene differentiation, histone modification, and miRNA biogenesis were the notable molecular mechanisms inferred. Long non-coding RNAs such as C058791.1, TTTY15 and TPTEP1 were predicted to be efficient in regulating the disease mechanisms. Drugs-F-1566-0341, Digoxin, Proscillaridin and Linifanib that reverse the gene expression signatures were predicted from drug perturbations analysis. The binding efficiency and interaction of proscillaridin and digoxin as obtained from the molecular docking studies confirmed their therapeutic potential. Two overlapping upregulated genes MDH1, SGCE and one downregulated gene PFKFB3 were appraised as potential biomarkers candidates. The upregulation of PGM5, ISLR and ANK2 as measured from their expressions in normal lungs affirmed their possible prognostic biomarker competence. The study explored significant insights for better diagnosis, and therapeutic options for COVID-19.

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Section: Resultsmentioning

confidence: 99%

Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19

Aishwarya

Gunasekaran

Margret³

2020

Journal of Biomolecular Structure and Dynamics

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“…Zebrafish possess a remarkable ability to regenerate lost neurons in response to acute injury ( Nagashima and Hitchcock, 2021 ) and it remains unclear why mutants with progressive, chronic degeneration, such as cep290 and bbs2 , fail to initiate a regenerative response. Transcriptional changes in response to acute damage to the zebrafish retina have been extensively documented ( Kassen et al, 2007 ; Ramachandran et al, 2012 ; Sifuentes et al, 2016 ; Mitchell et al, 2019 ; Hoang et al, 2020 ; Kramer et al, 2021 ), while only a limited number of studies have examined transcriptional changes in retinal degeneration mutants ( Morris et al, 2011 ; Saddala et al, 2020 ). The goals of this study were to identify transcriptional changes that were common between two models of retinal ciliopathies and to ascertain if those differences could provide insight on the reasons why these mutants do not exhibit signs of regeneration.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of transcriptional changes in zebrafish cep290 and bbs2 mutants by RNA-seq reveals upregulation of inflammatory and stress-related pathways

Grabinski

Parsana

2023

Front. Mol. Neurosci.

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Acute injury to the adult zebrafish retina triggers the release of pro-inflammatory cytokines and growth factors that stimulate multiple gene regulatory networks, which ultimately stimulate Müller glia to proliferate and regenerate neurons. In contrast, zebrafish carrying mutations in cep290 or bbs2 undergo progressive loss of cone photoreceptors and exhibit signs of microglia activation and inflammation, but the mutants fail to stimulate a regeneration response. To identify transcriptional changes that occur in zebrafish mutants undergoing progressive photoreceptor degeneration, RNA-seq transcriptional profiling was performed on cep290−/− and bbs2−/− retinas. The PANTHER Classification System was used to identify biological processes and signaling pathways that were differentially expressed between mutants and wild-type siblings during degeneration. As expected, genes associated with phototransduction were downregulated in cep290 and bbs2 mutants compared to wild-type siblings. Although both cep290 and bbs2 mutants undergo proliferation of rod precursors in response to retinal degeneration, the process of negatively regulating proliferation is enriched for upregulated genes, and this negative regulation may restrict proliferation of Müller glia and inhibit regeneration. A total of 815 differentially expressed genes (DEGs) were shared by cep290 and bbs2 retinas. Genes in pathways associated with inflammation, apoptosis, stress response, and PDGF signaling were overrepresented. Identifying the genes and biological pathways that are common in zebrafish models of inherited retinal degeneration provides a foundation for future studies on the mechanisms that regulate cell death as well as processes that prohibit Müller cell reprogramming or proliferation in a model capable of retinal regeneration. The pathways will provide targets for future interventions that may promote successful regeneration of lost photoreceptors.

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“…The gene ontology for proteomics and microarray was performed using FunRich and PANTHER. , Gene IDs of the identified list of genes and proteins were recovered and were applied using the online databases to identify the pathways and for comparison analysis. Protein–protein interactions were studied in the STRING online database at the highest confidence level of 0.9.…”

Section: Methodsmentioning

confidence: 99%

Graphitic Carbon Nitride Causes Widespread Global Molecular Changes in Epithelial and Fibroblast Cells

et al. 2021

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For scaffold and imaging applications, nanomaterials such as graphene and its derivatives have been widely used. Graphitic carbon nitride (g-C 3 N 4 ) is among one such derivative of graphenes, which draws strong consideration due to its physicochemical properties and photocatalytic activity. To use g-C 3 N 4 for biological applications, such as molecular imaging or drug delivery, it must interact with the epithelium, cross the epithelial barrier, and then come in contact with the extracellular matrix of the fibroblast cells. Thus, it becomes essential to understand its molecular mechanism of action. Hence, in this study, to understand the molecular reprogramming associated with g-C 3 N 4 , global gene expression using DNA microarrays and proteomics using tandem mass tag (TMT) labeling and mass spectrometry were performed in epithelial and fibroblast cells, respectively. Our results showed that g-C 3 N 4 can cross the epithelial barrier by regulating the adherens junction proteins. Further, using g-C 3 N 4 –PDMS scaffolds as a mimic of the extracellular matrix for fibroblast cells, the common signaling pathways were identified between the epithelium and fibroblast cells. These pathways include Wnt signaling, integrin signaling, TGF-β signaling, cadherin signaling, oxidative stress response, ubiquitin proteasome pathway, and EGF receptor signaling pathways. These altered signature pathways identified could play a prominent role in g-C 3 N 4 -mediated cellular interactions in both epithelial and fibroblast cells. Additionally, β catenin, EGFR, and MAP2K2 protein–protein interaction networks could play a prominent role in fibroblast cell proliferation. The findings could further our knowledge on g-C 3 N 4 -mediated alterations in cellular molecular signatures, enabling the potential use of these materials for biological applications such as molecular imaging and drug delivery.

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RNA-Seq reveals differential expression profiles and functional annotation of genes involved in retinal degeneration in Pde6c mutant Danio rerio

Cited by 7 publications

References 56 publications

Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19

Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19

Comparative analysis of transcriptional changes in zebrafish cep290 and bbs2 mutants by RNA-seq reveals upregulation of inflammatory and stress-related pathways

Graphitic Carbon Nitride Causes Widespread Global Molecular Changes in Epithelial and Fibroblast Cells

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