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Network analysis reveals strain-dependent response to misfolded tau aggregates (NanoString)

ABSTRACT: To investigate the effect of wild-derived genetic background on modeling tau aggregation, we injected either AAV-eGFP or AAV-hTauP301L into postnatal day 0 mice to drive widespread expression. We then performed gene expression profiling analysis using data obtained from Nanostring nCounter Mouse Neuroinflammation Panel from mouse brain cortex of 6 month old hTauP301L- or eGFP-mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE233988 | GEO | 2023/07/25

REPOSITORIES: GEO

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Network analysis reveals strain-dependent response to misfolded tau aggregates

Project description:To investigate the effect of wild-derived genetic background on modeling tau aggregation, we injected either AAV-eGFP or AAV-hTauP301L into postnatal day 0 mice to drive widespread expression. We then performed gene expression profiling analysis using data obtained from mRNA-seq from mouse brain cortex of 6 month old hTauP301L- or eGFP-mice.

2023-07-25 | GSE223840 | GEO

Network analysis reveals strain-dependent response to misfolded tau aggregates (NanoString)

Project description:Network analysis reveals strain-dependent response to misfolded tau aggregates (NanoString)

| PRJNA979158 | ENA

Phosphoproteomics of tau from tau knockout mice expressing tau in hippocampal neurons during spatial reference learning

Project description:This dataset describes the mass spectrometric identification of phosphorylation sites on tau protein isolated from the hippocampus of tau knockout (tau‑/‑) mice during spatial reference learning. Tau expression was selectively reintroduced into hippocampal neurons using adeno‑associated viral (AAV) vectors to enable controlled investigation of tau phosphorylation under defined behavioural conditions. Tau‑/‑ mice received bilateral injections into the dorsal and ventral hippocampus with either AAV‑syn1‑d2tTA‑tau or the control vector AAV‑syn1‑d2tTA‑eGFP. Following postoperative recovery, mice were trained in a spatial reference learning paradigm (day 2 of Morris water maze). Temporal control of tau or eGFP expression was achieved using the doxycycline-regulated d2tTA system, with induction on day 2 of training. Hippocampal tissue was collected at this time point for biochemical analysis. Tau protein was immunoprecipitated from hippocampal lysates and subjected to bottom‑up proteomic analysis. Immunoprecipitated material was reduced, alkylated, and digested with trypsin. Phosphopeptides were subsequently enriched using titanium dioxide (TiO₂) affinity chromatography. Enriched phosphopeptides underwent buffer exchange, vacuum centrifugation, and resuspension prior to liquid chromatography–tandem mass spectrometry (LC‑MS/MS) analysis.

2026-04-10 | PXD076789 | Pride

Increased G3BP2-Tau interaction in Tauopathies is a natural defense against Tau aggregation

Project description:Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress granules, directly interacts with Tau and inhibits Tau aggregation. In the human brain, the interaction of G3BP2 and Tau is dramatically increased in multiple Tauopathies and precedes neurofibrillary tangle (NFT) formation in Alzheimer’s disease (AD). Surprisingly, Tau pathology is significantly elevated upon loss of G3BP2 in human neurons and brain organoids. Moreover, we find that G3BP2 masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. Our study defines a novel role for RBPs as a line of defense against Tau aggregation in Tauopathies.

2023-05-17 | GSE226624 | GEO

Phosphoproteomics of tau from tau knockout mice expressing tau or phospho-deficient tauT205A in active hippocampal cells upon fear conditioning

Project description:This dataset describes the mass spectrometric identification of tau phosphorylation sites in hippocampal neurons active during fear memory encoding. Tau knockout (tau‑/‑) mice were used as a background to selectively express human 2N4R tau variants in behaviourally activated neuronal populations. Tau‑/‑ mice received bilateral injections into the dorsal and ventral hippocampus with doxycycline‑regulated AAV vectors under control of the robust activity‑marking (RAM) promoter. Experimental groups expressed either wild‑type human 2N4R tau (tauWT; n = 4), a phosphorylation‑deficient tau mutant (tauT205A; n = 4), or eGFP as a negative control (n = 2). Following postoperative recovery, mice underwent fear conditioning. Hippocampal tissue was collected 120 minutes after conditioning, prior to induction of transgene expression. Temporal control of tau, tauT205A, or eGFP expression was achieved by doxycycline withdrawal, allowing expression during a defined 20‑hour window corresponding to neuronal activity associated with fear memory encoding. Tau protein was subsequently immunoprecipitated from hippocampal lysates and subjected to bottom‑up phosphoproteomic analysis. Immunoprecipitated tau was reduced, alkylated, and digested with trypsin, followed by enrichment of phosphopeptides using titanium dioxide (TiO₂) affinity chromatography. Enriched phosphopeptides were buffer‑exchanged, dried by vacuum centrifugation, resuspended, and analysed by liquid chromatography–tandem mass spectrometry (LC‑MS/MS). This dataset enables comparative analysis of tau phosphorylation patterns associated with neuronal activation during fear learning and provides insight into the role of the T205 phosphorylation site in activity‑dependent tau regulation.

2026-04-10 | PXD076837 | Pride

Nanostring gene expression profiling for markers of Alzheimer's disease in MAPT P301S;cTFEB;HSACre and MAPT P301S male and female mice

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

Tau aggregates are RNA-protein assemblies that mis-localize multiple nuclear speckle components

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

Network analysis reveals strain-dependent response to misfolded tau aggregates

Project description:Network analysis reveals strain-dependent response to misfolded tau aggregates

| PRJNA928503 | ENA

CCA NanoString data (60CCA)

Project description:Raw .RCC files for NanoString. nCounter PanCancer IO 360 Panel was used

| EGAD00010002612 | EGA

Comparison of microRNA Profiling Platforms (NanoString)

Project description:Global miRNA expression profiling of human malignancies is gaining popularity in both basic and clinically driven research. But to date, the majority of such analyses have used microarrays and quantitative real-time PCR. With the introduction of digital count technologies, such as next-generation sequencing (NGS) and the NanoString nCounter System, we have at our disposal, many more options. To make effective use of these different platforms, the strengths and pitfalls of several miRNA profiling technologies were assessed, including a microarray platform, NGS technologies and the NanoString nCounter System. These results were compared to gold-standard quantitative real-time PCR. Comparison of non-small cell lung cancer cell lines grown in vitro (n = 5) and in vivo (n = 5) as xenograft models.

2013-10-22 | E-GEOD-51504 | biostudies-arrayexpress

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