RNA-seq from USP10 and TDP-43 overexpression and TDP-43 knockdown associated with or without USP10 overexpression in HeLa cells
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PROVIDER: PRJEB97173 | ENA |
REPOSITORIES: ENA
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Project description:Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may exacerbate TDP-43 aggregation and neurodegeneration. Here we tested the effects of overexpression of GFP-taggted TDP-43 proteins in H4 cells, in the presence or ascence of the EIF2B activiting small molecule DNL343. Cytoplasmic TDP-43 expression caused upregulation of ISR gene transcripts, including MTHFD2, GDF15, SLC7A11, and ATF3, relative to the GFP expressing sample. Transcript level changes induced by GFP-TDP-43(86-414) were prevented by DNL343 treatment, with significant downregulation of ISR genes, including CHAC1, ATF4, and DDIT3.
2025-06-30 | GSE281957 | GEO
Project description:Cytoplasmic aggregation and nuclear depletion of TDP-43 are hallmarks of several age-related neurodegenerative disorders. Yet, recapitulating both features in cellular systems has been a major challenge. Here, we produced amyloid-like fibrils from the recombinant low-complexity-domain of TDP-43, and demonstrate that sonicated fibrils trigger TDP-43 pathology in human cell lines and iPSC-derived neurons. Fibril-induced cytoplasmic TDP-43 inclusions acquire distinct biophysical properties, recapitulate pathological hallmarks such as phosphorylation, ubiquitin- and p62-accumulation, and recruit nuclear endogenous TDP-43 leading to nuclear-loss-of-function-driven disease-specific cryptic splicing defects. Cytoplasmic TDP-43 aggregates exhibit, with time, distinct heterogeneous morphologies as in patients including compacted, filamentous or fragmented, through the activation of cellular protein clearance pathways. Cell-specific progressive toxicity is provoked by seeded TDP-43 pathology in human neurons. These findings identify templated aggregation of TDP-43 as a key mechanism driving both cytoplasmic gain- and nuclear-loss-of-function, offering a valuable approach to identify modifiers of sporadic TDP-43 proteinopathies.
2025-03-28 | GSE284828 | GEO
Project description:MicroRNAs (miRNAs) play important roles in a wide range of cellular processes. Aberrant regulation of miRNA genes contributes to human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a DNA/RNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs whose expression levels are regulated by TDP-43 using RNA-Seq coupled with siRNA-mediated knockdown approach. TDP-43 knocking down affected the expression of a number of miRNAs. Alterations in isomiR patterns and miRNA arm selection after TDP-43 knockdown suggest a role of TDP-43 in miRNA editing. We examined correlation of selected TDP-43 associated miRNAs and their candidate target genes in human cancers. Our data reveal highly complex roles of TDP-43 in regulating different miRNAs and their target genes. Our results suggest that TDP-43 may promote migration of lung cancer cells by regulating miR-423-3p expression. On the other hand, TDP-43 increases miR-500a-3p expression and binds to the mature miR-500a-3p sequence. Low expression of miR-500a-3p was associated with poor survival of lung cancer patients, suggesting that TDP-43 may have a suppressive role in cancer by regulating miR-500a-3p. Our experiments reveal that cancer-associated genes LIF and PAPPA may be targets of miR-500a-3p. Together with other studies, our work suggests that TDP-43-regulated miRNAs may play multi-facet roles in the pathogenesis of cancer. small RNA seq in SH-SY-5Y, SNB-19 and HT22 (TDP-43 siRNA VS Control siRNA)
2016-08-02 | E-GEOD-85065 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) play important roles in a wide range of cellular processes. Aberrant regulation of miRNA genes contributes to human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a DNA/RNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs whose expression levels are regulated by TDP-43 using RNA-Seq coupled with siRNA-mediated knockdown approach. TDP-43 knocking down affected the expression of a number of miRNAs. Alterations in isomiR patterns and miRNA arm selection after TDP-43 knockdown suggest a role of TDP-43 in miRNA editing. We examined correlation of selected TDP-43 associated miRNAs and their candidate target genes in human cancers. Our data reveal highly complex roles of TDP-43 in regulating different miRNAs and their target genes. Our results suggest that TDP-43 may promote migration of lung cancer cells by regulating miR-423-3p expression. On the other hand, TDP-43 increases miR-500a-3p expression and binds to the mature miR-500a-3p sequence. Low expression of miR-500a-3p was associated with poor survival of lung cancer patients, suggesting that TDP-43 may have a suppressive role in cancer by regulating miR-500a-3p. Our experiments reveal that cancer-associated genes LIF and PAPPA may be targets of miR-500a-3p. Together with other studies, our work suggests that TDP-43-regulated miRNAs may play multi-facet roles in the pathogenesis of cancer.
2016-08-02 | GSE85065 | GEO
Project description:Discovery of proteins and pathways affected by overexpression of the protein TDP-43 in neurons cultured from wild-type and mice homogygous for the transgene.
2023-04-27 | PXD014889 | Pride
Project description:The aim of this study is to understand the mechanisms of TDP-43 neurotoxicity. Here, we perform a RNA-Seq analysis in TDP-43 gain-of-fucntion (GOF) , TDP-43 loss-of-function and wild-type late pupae heads (73-90 hours APF) and perform TDP-43 GOF vs wild type and TDP-43 LOF vs wild-type differential expression analysis to show that both mechanisms presents defects in ecdysone receptor (ECR)-dependeint transcriptional program switching, and strongly deregulate expression from the neuronal microtubule associated protien Map205. RNA-seq was performed in two wild-type D.melanogaster biological replicates (Canton S, w1118 ), four biological replicates for TDP-43 (LOF) with two distinct genotypes (dTDP-43Δ142/Df(2R)106,dTDP-43Δ23/Δ142 ) and two TDP-43 GOF biological replicates (act5c>dTDP-43 ).
2013-01-22 | E-GEOD-42844 | biostudies-arrayexpress
Project description:TDP-43 is an important RNA binding protein. To better understand its binding targets in human neurons, we performed TDP-43 iCLIP on SHSY5Y cells.
2022-02-02 | E-MTAB-11243 | biostudies-arrayexpress
Project description:Purpose: The goal of this stuydy was to apply transcriptome profiling (RNA-seq) to human cells that either express or which lack the TDP-43 protein. Methods: mRNA profiles of TDP-43 KO HeLa cells and "rescued" TDP-43 KO cells wherein a wildtype TDP-43 transgene was re-expressed at endogenous levels were generated by deep sequencing, in triplicate, on Illumina’s HiSeq 2500 using 2x70bp paired-end reads, generating 104.4-128.2 million reads (52.2-64.1 million pairs) per sample. . The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat2 followed by Cufflinks Cuffmerge and Cuffdiff to define transcripts and establish their abundance and finally to perform differential gene expression analysis, using the assembled known plus novel transcripts . Results: Using an optimized data analysis workflow, we mapped approximately 50-60 million reads per sample to the human genome (build hg19) and identified transcripts whose abundance differed between the TDP-43 KO versus "rescued" conditions. Conclusions: Our study presents a detailed analysis of the impact of the knockout of TDP-43 on the transcriptome of a human cell line. The results reported here should provide a framework for defining transcripts whose abundnace and splicing are regulated by TDP-43.
2019-09-09 | GSE136366 | GEO
Project description:Identifications of proteins interacting with TDP-43 or linear fusions of mono- or tetra-SUMO2 with TDP-43.
2025-09-08 | PXD050322 | Pride
Project description:The aim of this study is to understand the mechanisms of TDP-43 neurotoxicity. Here, we perform a RNA-Seq analysis in TDP-43 gain-of-fucntion (GOF) , TDP-43 loss-of-function and wild-type late pupae heads (73-90 hours APF) and perform TDP-43 GOF vs wild type and TDP-43 LOF vs wild-type differential expression analysis to show that both mechanisms presents defects in ecdysone receptor (ECR)-dependeint transcriptional program switching, and strongly deregulate expression from the neuronal microtubule associated protien Map205.
2013-01-22 | GSE42844 | GEO