Ontology highlight
ABSTRACT:
PROVIDER: PRJNA544101 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9104862_1.fastq.gz | Fastqsanger.gz | |||
| SRR9104862_2.fastq.gz | Fastqsanger.gz |
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Project description:We report the isolation and sequencing of tau aggregates from [1] HEK293 cells expressing Tau-RD-P301S-CFP/YFP that have been seeded with preformed fibrils from the brain of P301S mice (B6-Tg(Thy1-MAPT*P301S)2541; referred to as Tg2541 mice). Tau aggregates were isolated by differential centrifugation followed by fluorescence automated particle sorting using a BD FACSaraia. We found that these tau aggregates were enriched for particular small non-coding RNAs, including snoRNAs and snRNAs. [2] the following mice: FvBB6F1-Tg(Camk2a-tTa),(tetO-MAPT*wt)21221 (referred to as rTg21221 or WT tau mice in the paper) and FvBB6F1-Tg(Camk2a-tTA)1Mmay, (tet)-tdTomato-Syp/EGFP)1.1Luo/J,(tetO-MAPT*P301L)4510 (referred to as rTg4510 or P301L mice in the paper). Briefly, tau aggregates were isolated by 1% sarkosyl extraction (to enrich for insoluble proteins) followed by immunoprecipitation of tau using the tau-12 antibody (see Methods section of associated paper for further details). We found that these tau aggregates were enriched for particular small non-coding RNAs, including snRNAs and some snoRNAs. [3] Sequencing of HEK293 tau biosensor cells with and without tau aggregates reveals evidence of significant splicing alterations. Specifically we observed an increase in intron retention events in cells that contain tau aggregates relative to cells without tau aggregates.
2021-04-06 | GSE148716 | GEO
Project description:The development of an effective therapy against tauopathies like Alzheimer’s disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization. Altogether, these tau mutant iPSC lines allow us to study IVS10+16 and P301S mutations in an isogenic background and to unravel a potential link between pathogenic 4R tau expression and FTDP-17.
2018-08-01 | GSE106075 | GEO
Project description:The development of an effective therapy against tauopathies like Alzheimer’s disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization. Altogether, these tau mutant iPSC lines allow us to study IVS10+16 and P301S mutations in an isogenic background and to unravel a potential link between pathogenic 4R tau expression and FTDP-17.
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Project description:Alzheimer’s disease is known to alter astrocytes, but the effect of Aß and Tau pathology on these cells remains poorly understood. We investigated the transcriptomic behaviour of astrocytes (via translating ribosome affinity purification (TRAP)), and bulk brain tissue, in mouse models of APP/PS1 ß-amyloidopathy and MAPT-P301S tauopathy, in a mouse model overexpressing cytoprotective Nrf2 specifically in astrocytes (GFAP-Nrf2 model), and in crosses between the amyloidopathy and tauopathy models with the GFAP-Nrf2 mouse.
2021-12-02 | E-MTAB-10985 | biostudies-arrayexpress
Project description:Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to lack of appropriate human models. Here, we engineered new human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer’s Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
2024-04-08 | GSE255904 | GEO
Project description:Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to lack of appropriate human models. Here, we engineered new human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer’s Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
2024-04-08 | GSE255902 | GEO
Project description:To explore whether tau-related epigenomic changes that we found human brain H3K9ac data (Synapse ID: syn4896408) are recapitulated in mouse models known to accumulate tau, we generated hippocampal H3K9ac ChIP-seq profiles from two different mouse models each at an early and a late stage of neurodegeneration. Specifically, we studied 6 and 11 months old mutant tau mice (MAPT P301S), which start to accumulate phosphorylated tau in neurons by 6 months. Wild-type mice of the same age were used as controls. The second mouse model was the CK-p25 model, which is characterized by increased amyloid-β levels early after p25 induction followed by increased tau phosphorylation and neuronal loss at later stages. Three months old CK-p25 mice were studied 2 weeks and 6 weeks after p25 induction and compared with CK littermate controls.
2018-12-07 | GSE97560 | GEO
Project description:To assess the potential neuroprotective effects of overexpressing skeletal muscle Transcription Factor EB (TFEB) signaling in the context of age-associated neurodegenerative disease pathologies, we derived cTFEB;HSACre transgenic mice in the MAPT P301S tau hyperphosphorylated background and used the Nanostring nCounter® Alzheimer’s Disease panel to gain more precise insights into disease-relevant transcriptional changes in the hippocampus in both male and female mice with both Tau hyperphosphorylation and skeletal muscle TFEB overexpression. We confirmed significantly reduced transcriptional activation of the nCounter AD microglial activation module through signature scoring.
2024-02-14 | GSE242362 | GEO
Project description:Tau (MAPT) is a microtubule-associated protein causing frequent neurodegenerative diseases or inherited frontotemporal lobar degenerations. Emerging evidence for non-canonical functions of Tau in DNA protection and P53 regulation suggests its involvement in cancer. Indeed, Tau expression correlates with cancer-specific survival or response to microtubule therapeutics. These data may imply common molecular pathways involved in the pathogenesis of neurodegenerative disorders and cancer. To bring new evidence that Tau represents a key protein in cancer, we present an in silico pan-cancer analysis of MAPT transcriptomic profile in over 11000 clinical samples and over 1300 pre-clinical samples provided by the TCGA and the DEPMAP datasets respectively. We completed this analysis by exploring a possible interplay of MAPT with wild-type or mutated P53. Then, we calculated the impact of MAPT expression on clinical outcome and drug response. Overall, the results support a relevant role of the MAPT gene in several cancer types, although the contribution of Tau to cancer appears to very much depend on the cellular context.
2022-11-27 | E-MTAB-8166 | biostudies-arrayexpress
Project description:Tau is encoded by MAPT and abnormal aggregates of tau are a hallmark of a group of neurodegenerative diseases called tauopathies. MAPT is lowly expressed in neural progenitor cells (NPCs), but it is more highly expressed in oligodendrocytes, astrocytes, and neurons that derive from NPCs. This expression switch at differentiation suggests that MAPT expression is controlled by transcription factors and cis-regulatory elements specific to these differentiated cell types, including neurons.
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