Browse
Submit Data
Databases
API
Help

Dataset Information

33 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of alpha-crystallin gene knockout on zebrafish lens development

ABSTRACT: The alpha-crystallin small heat shock proteins contribute to the transparency and refractive properties of the vertebrate eye lens and prevent the protein aggregation that would otherwise produce lens cataract, the leading cause of human blindness. There are conflicting data in the literature as to what role that alpha-crystallins may play in early lens development. In this study we used CRISPR gene editing to produce zebrafish lines with null mutations for each of the three alpha-crystallin genes (cryaa, cryaba and cryabb). Absence of protein was confirmed by mass spectrometry and lens phenotypes were assessed with differential interference contrast microscopy and histology. Loss of alpha A-crystallin produced a variety of lens defects with varying severity in larval lenses at 3 and 4 dpf, but little significant change in normal fiber cell denucleation. Loss of either Alpha Ba- or Alpha Bb-crystallin produced no significant lens defects. Mutation of each Alpha-crystallin gene did not alter the expression levels of the remaining two, suggesting a lack of genetic compensation. These data confirm a developmental role for Alpha A-crystallin in lens development, but the range of phenotype severity suggests its loss simply increases the chance for defect, and that the protein is not essential. Our finding that cryaba and cryabb null mutants lack noticeable lens defects is congruent with insignificant transcript levels in lens epithelial and fiber cells. Future experiments can explore the molecular consequences of cryaa mutation and causes of lens defects in this null mutant, as well as the roles of other genes in lens development and function.

ORGANISM(S): Danio Rerio

SUBMITTER: Ashok Reddy

PROVIDER: PXD030918 | panorama | Thu Jan 20 00:00:00 GMT 2022

REPOSITORIES: PanoramaPublic

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of mouse ovaries from Lhx8 Null newborns

Project description:Lhx8 is a homeobox gene expressed in oocytes and critical in oogenesis. Lhx8 deficiency leads to rapid loss of postnatal oocytes. Early oocyte differentiation is poorly understood. We hypothesized that lack of Lhx8 perturbs global expression of genes preferentially expressed in oocytes. We compared Lhx8 knockout and wild type ovaries using Affymetrix 430 2.0 microarray platform. Experiment Overall Design: Each array was hybridized with cRNA produced from pooled total RNA from at least 25 specimens. The experiment was performed with 3 replicates. The results from these three arrays was compared to arrays hybridized with cRNA produced from pooled total RNA from at least 25 wild type specimens of the same genetic background.

2008-06-15 | E-GEOD-7774 | biostudies-arrayexpress

Generation of Human Islet Cell-Type-Specific Identity Genesets

Project description:Generation of mature cells with stable functional identities is crucial for developing cell-based replacement therapies. Current global efforts to produce insulin-secreting beta-like cells to treat diabetes are hampered by the lack of tools to reliably assess cellular identity. We conducted a thorough single-cell transcriptomics meta-analysis to generate robust genesets defining the identity of human adult alpha-, beta-, gamma- and delta-cells. After extensive validation, we showed the efficacy of the novel genesets to define changes in islet cell identity, whether during embryonic development or in different experimental setups aimed at developing new functional glucose-responsive insulin-secreting cells, such as through pluripotent stem-cell differentiation or islet cell reprogramming protocols. Finally, we evaluated whether the perturbed metabolic conditions typical of diabetes influence islet cell identity. We observed that alpha-cells from diabetic donors exhibit an altered phenotype. In conclusion, these novel genesets represent valuable tools that robustly benchmark gain and loss in islet cell identity traits.

2021-06-26 | GSE150724 | GEO

Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module

Project description:Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in PBMCs from hospitalized patients infected with either the Alpha variant (n=36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n=13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Alpha (n=9) and Gamma (n=3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.

2022-02-23 | GSE190680 | GEO

The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony

Project description:Commitment to and completion of sexual development are essential for Toxoplasma gondii to produce oocysts in the intestine of the feline host. Understanding of the molecular mechanism responsible for sexual commitment is extremely limited due to the lack of model systems. Here, we show that the transcription factors AP2XI-2 and AP2XII-1 associated with the epigenetic repressors MORC/HDAC3 complex are constitutively expressed in both tachyzoite and bradyzoite stages but not in the merozoite stage. Depletion of AP2XI-2 or AP2XII-1 elicits the expression of genes specific to merozoites, but they play different roles in the merogony process. Depletion of AP2XI-2 in type II Pru strain induced parasites to undergo merogony and produce mature merozoites in alkaline medium but not in neutral medium, whereas the AP2XII-1 depleted Pru strain underwent several rounds of schizogony and produced merozoites in neutral medium and more markedly under alkaline conditions. Furthermore, we show that two AP2XI-2 interacting proteins are also involved in repressing merozoite programming. Overall, these findings indicate that the merozoite primed pre-sexual commitment is controlled by an intricate regulatory network and that AP2XI-2 or AP2XII-1 depleted parasites can be used as a model to study the merogony in vitro.

2023-12-20 | PXD043808 | Pride

Caveolin1 Deficiency: A Type I Endothelial Interferonopathy Associated with Pulmonary Arterial Hypertension

Project description:CAV1 loss-of-function mutations have been associated with the development of pulmonary arterial hypertension (PAH). CAV1 is an integral component of endothelial caveolae, specialized lipid rafts that attach to the actin cytoskeleton and modulate receptor/signal transduction coupling. CAV1 loss in pulmonary artery endothelial cells produced a proliferative, hypermigratory cellular phenotype with a disrupted cytoskeletal architecture, mirroring known features of PAH pathobiology. Gene expression on Human Pulmonary Arterial Endothelial Cells (PAECs) transfected with non-targeting siRNA control pool or siRNA (ON-TARGET plus CAV1) in the presence or absence of TNF-alpha was evaluated

2021-02-24 | GSE138991 | GEO

GPNMB confers risk for Parkinson’s disease through interaction with alpha-synuclein

Project description:Many risk loci for Parkinson’s disease (PD) have been identified by genome-wide association studies (GWAS), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel SNP rs199347) to GPNMB, through colocalization analyses of expression quantitative trait locus (eQTL) and PD risk signals, confirmed by allele-specific expression studies in human brain. In cells, Glycoprotein Nonmetastatic Melanoma Protein B protein (GPNMB) co-immunoprecipitated and co-localized with alpha-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of GPNMB resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 781 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating with disease severity. Thus, GPNMB represents a PD risk gene, with potential for biomarker development and therapeutic targeting.

2022-06-17 | GSE206327 | GEO

Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma

Project description:Pheochromocytoma has attracted much attention as a kind of neuroendocrine tumor with the highest genetic correlation in all types of tumors. Detailedly, the frequency of germline mutation in pheochromocytoma is as high as about 40%, and the mutation frequency of von Hippel Lindau (VHL) is the highest in all pheochromocytoma genes. However, the effects of VHL mutation on proteome of pheochromocytoma have remained unexplored. In this study, we compared and analyzed the proteomics of VHL-deficient and VHL WT PC12 cell line. It is showed that expressional level of 434 proteins (fold change > 1.3, VHL shRNA/WT) was significantly changed by VHL deficiency. Furthermore, the functions of these proteins were predicted by gene ontology (GO) and Kyoto Protocol Encyclopedia of Genes and Genomes (KEGG). Of the 434 proteins, 83 proteins, involved in cell proliferation, cell cycle, cell migration, and so on, were interpreted their complex regulatory relationships using String database. More importantly, we discovered 7 novel critical genes whose expression were up-regulated due to VHL deficiency, including Connective Tissue Growth Factor (CTGF), Syndecan Binding Protein (SDCBP), Cysteine Rich Protein 61 (CYR61/CCN1), Collagen Type III Alpha 1 Chain (COL3A1), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type V Alpha 2 Chain (COL5A2) and Serpin Family E Member 1 (SERPINE1), which may be related to cell proliferation and migration in VHL-mutated pheochromocytoma tumor samples. These results indicate that deficiency of VHL would promote the development of pheochromocytoma by activating expression of genes associated with cell proliferation and migration.

2021-03-11 | PXD021190 | Pride

Polymorphic Histidine-rich Glycoprotein LC-MS/MS

Project description:Histidine-rich glycoprotein (HRG) HRG is a liver-produced protein circulating in human plasma serum at high concentrations of around 125 ug/mL. HRG belongs to the family of type-3 cystatins and has been implicated in a plethora of biological processes, albeit its precise function is still not well understood. Human HRG is a highly polymorphic protein, with at least 5 variants with minor allele frequencies (MAF) of more than 10%, variable in populations from different parts of the world. Considering these 5 mutations we can expect already 35 = 243 possible possibly genetic HRG variants in the population. Here, we purified HRG from serum of 44 individual donors and investigated by proteomics the occurrence of different allotypes, each being either homozygote or heterozygote for each of the 5 mutation sites. We observed that some mutational combinations in HRG were highly favored, while others were apparently missing, although they ought to be present based on the stochastic independent assembly of these 5 mutation sites. To further explore this behavior, we extracted data from the 1000 genome project (n ~ 2500 genomes) and assessed the frequency of different HRG mutants in this larger dataset, observing a prevailing agreement with our proteomics data. From all the proteogenomic data we conclude that the 5 different (frequent) mutations sites in HRG are not occurring independently, but some mutational variants at different sites are fully mutually exclusive, whereas other are highly intwined. Specific mutations also affect HRG abundance and its glycosylation. As the levels of HRG have been suggested as a protein biomarker in a variety of biological processes (e.g., aging, COVID-19 severity, severity of bacterial infections), we here conclude that the highly polymorphic nature of the protein needs to be considered in such evaluations, as these mutations affect HRG’s abundance, structure, post-translational modifications, and function.

2023-10-24 | PXD040914 | Pride

Expression data from E15.5 mouse embryos

2015-10-30 | GSE62834 | GEO

Expression data from E15.5 mouse embryos

Project description:The pancreatic beta cells are the only cells that can produce insulin in response to prevailing glycemia. The development of beta cells was found to be depending on the activity of a complex genetic network. Overexpression of transcriptional factor MafK in beta cells have resulted in impairment of thier functions and suppressed insulin secretion and increased the severity of beta cell loss resulting in an overt diabetes. We used microarrays to study the changes in islet gene expression profiles in MafK Tg. Mafk overexpression was expected to disrupt functions of genes containing MARE sites in their regulatory regions by bindig to cis-regulatory elements. Exploration of new factors with sunctional MAREs in thier regulatory regions in beta cells will improve our targeting stratigies for treatment of diabetes. A 0.78 kb full-length cDNA encoding the murine MafK protein including a FLAG peptide at the N-terminus was inserted into the rat insulin I promoter. Then, the construct was injected into BDF1-fertilized eggs to generate transgenic mice. All Tg mice were maintained on an ICR genetic background. Whole pancreata were collected from MafK transgenic embryos as well as wild type embryos at E15.5 (N=3 per each gentype). Total RNA was extracted and hybridized for Affymetrix microarray analysis.

2015-10-30 | E-GEOD-62834 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data