Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration

ABSTRACT: Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration

PROVIDER: PRJNA1008150 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25729600_1.fastq.gz	Fastqsanger.gz
	SRR25729600_2.fastq.gz	Fastqsanger.gz
	SRR25729601_1.fastq.gz	Fastqsanger.gz
	SRR25729601_2.fastq.gz	Fastqsanger.gz
	SRR25729602_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration

Project description:Aging is a common risk factor in neurodegenerative disorders and the ability to investigate aging of neurons in an isogenic background would facilitate discovering the interplay between neuronal aging and onset of neurodegeneration. Here, we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs), a primary neuronal subtype affected in Huntington's disease (HD), identified pathways associated with RCAN1, a negative regulator of calcineurin. Notably, RCAN1 undergoes age-dependent increase at the protein level detected in reprogrammed MSNs as well as in human postmortem striatum. In patient-derived MSNs of adult-onset HD (HD-MSNs), counteracting RCAN1 by gene knockdown (KD) rescued HD-MSNs from degeneration. The protective effect of RCAN1 KD was associated with enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, which in turn dephosphorylates and promotes nuclear localization of TFEB transcription factor. Furthermore, we reveal that G2-115 compound, an analog of glibenclamide with autophagy-enhancing activities, reduces the RCAN1-Calcineurin interaction, phenocopying the effect of RCAN1 KD. Our results demonstrate that RCAN1 is a potential genetic or pharmacological target whose reduction-of-function increases neuronal resilience to neurodegeneration in HD through chromatin reconfiguration.

2023-10-10 | GSE241430 | GEO

Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration.

Project description:Aging is a common risk factor in neurodegenerative disorders. Investigating neuronal aging in an isogenic background stands to facilitate analysis of the interplay between neuronal aging and neurodegeneration. Here we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs) in Huntington's disease identified pathways involving RCAN1, a negative regulator of calcineurin. Notably, RCAN1 protein increased with age in reprogrammed MSNs as well as in human postmortem striatum and RCAN1 knockdown rescued patient-derived MSNs of Huntington's disease from degeneration. RCAN1 knockdown enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, leading to TFEB's nuclear localization by dephosphorylation. Furthermore, G2-115, an analog of glibenclamide with autophagy-enhancing activities, reduced the RCAN1-calcineurin interaction, phenocopying the effect of RCAN1 knockdown. Our results demonstrate that targeting RCAN1 genetically or pharmacologically can increase neuronal resilience in Huntington's disease.

| S-EPMC11456361 | biostudies-literature

Longitudinal modeling of human neuronal aging identifies RCAN1-TFEB pathway contributing to neurodegeneration of Huntington's disease.

| S-EPMC10197783 | biostudies-literature

A TFEB nuclear export signal integrates amino acid supply and glucose availability

Project description:How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3 phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognised nuclear export signal (NES). Importantly, GSK3 is inactivated by AKT in response to mTORC2 signalling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle.

2018-10-18 | PXD009677 | Pride

Transcriptome analysis of control and TFEB/TFE3 DKO RAW264.7 in response to DNA Damage

Project description:We analyze the contribution of the transcription fators TFEB and TFE3 to the DNA Damage Response (DDR)

2018-09-30 | GSE118517 | GEO

Transcriptome analysis of control and TFEB/TFE3 DKO MEFs in response to DNA Damage

Project description:We analyze the contribution of the transcription fators TFEB and TFE3 to the DNA Damage Response (DDR)

2018-09-30 | GSE118516 | GEO

Expression data from injected mice overexpressing TFEB specifically in liver

Project description:In order to identify the effects of transcription factor EB (TFEB) overexpression on the liver transcriptome, we performed Affymetrix GeneChip hybridization experiments on injected mice overexpressing TFEB specifically in the liver. For the analysis of the injected mice overexpressing TFEB, total RNA was extracted from the liver of three mice. RNA extracted from the liver of 3 not-injected mice was used as a control.

2013-04-20 | E-GEOD-35015 | biostudies-arrayexpress

Profiling gene expression in HeLa cells following TFEB transient transfection

Project description:Total RNA samples from three biological replicates in which TFEB was transiently overexpressed in HeLa cells by transfection using a pcDNA3 vector. As negative control, we used total RNA samples from HeLa cells transfected with an empty pcDNA3 vector. TFEB transfection

2010-04-09 | E-GEOD-16267 | biostudies-arrayexpress

TFEB Immunoprecipitation And Proteome

Project description:Our studies in Salmonella Typhimurium (S. Typhimurium)-infected cells indicate that TFEB has a non-transcriptional, cytosolic function in addition to its well-characterized role as a transcription factor in regulating autophagy and lysosome biogenesis. An unbiased proteomics approach revealed that TFEB interacts with several mitochondrial proteins, which is lost when infected with S. Typhimurium. Microscopical and biochemical examinations further confirmed a novel localization of TFEB in mitochondria. We have also identified a TOMM20 binding motif within the protein sequence of TFEB which, facilitates the mitochondrial translocation in a mTOR-dependent manner. Our results further demonstrate that TFEB and the mitochondrial protease LonP1 co-regulate the assembly of complex I and its function. Moreover, during S. Typhimurium infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines.

2024-05-21 | PXD013758 | Pride

Transcriptome analysis of the injected Ppara-KO mice overexpressing TFEB specifically in liver

Project description:Expression data from Ppara (peroxisome proliferator activated receptor alpha) KO mice injected with TFEB specifically in liver. In order to identify the effects of TFEB overexpression together with Ppara absence on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the injected mice For the analysis on the injected Ppara-KO mice overexpressing TFEB, total RNA was extracted from the liver of three mice; RNA extracted from the liver of not-injected mice was used as control.

2013-04-20 | E-GEOD-41140 | 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