Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alterations in DNA replication timing identify TP63 as a novel marker of progeroid diseases [RepliSeq]

ABSTRACT: Progeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Despite identification of causal mutations, mechanisms that generate their clinical manifestations remain elusive. Here, we identified a DNA replication timing (RT) signature that distinguishes progeroid syndromes from normal aging and identifies TP63 gene as a new disease marker. Abnormal TP63 RT appears early during differentiation of progeroid iPSCs and is associated with altered gene variant expression. Our findings demonstrate the utility of RT signatures to identify novel biomarkers not detected by other methods, reveal abnormal TP63 RT as an early event in progeroid disease progression and offer TP63 gene regulation as a potential therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98472 | GEO | 2017/11/16

SECONDARY ACCESSION(S): PRJNA385173

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Alterations in DNA replication timing identify TP63 as a novel marker of progeroid diseases [Chip]

Project description:Progeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Despite identification of causal mutations, mechanisms that generate their clinical manifestations remain elusive. Here, we identified a DNA replication timing (RT) signature that distinguishes progeroid syndromes from normal aging and identifies TP63 gene as a new disease marker. Abnormal TP63 RT appears early during differentiation of progeroid iPSCs and is associated with altered gene variant expression. Our findings demonstrate the utility of RT signatures to identify novel biomarkers not detected by other methods, reveal abnormal TP63 RT as an early event in progeroid disease progression and offer TP63 gene regulation as a potential therapeutic target.

2017-11-16 | GSE98471 | GEO

DNA methylation in progeroid syndromes

Project description:DNA methylation in progeroid syndromes

| PRJNA544684 | ENA

Alterations in DNA replication timing identify TP63 as a novel marker of progeroid diseases

Project description:Alterations in DNA replication timing identify TP63 as a novel marker of progeroid diseases

| PRJNA385178 | ENA

LINE-1 RNA is causative of heterochromatin erosion and target for amelioration of senescent phenotypes in progeroid syndromes

2022-11-02 | PXD032944 | Pride

Lifespan extension by diet restriction in DNA repair deficient progeroid Ercc1Δ/- mice [mRNA]

Project description:DNA repair-deficient Ercc1Δ/- mice show premature cell death, senescence and numerous accelerated aging features limiting lifespan to 4-6 month. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR). Here we report that subjecting these progeroid, dwarf mutants to actual dietary restriction (DR) resulted in the largest lifespan increase recorded in mammals. Thirty percent DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function. The DR response in Ercc1Δ/- mice resembled DR in wild type animals including reduced insulin signaling. Interestingly, ad libitum Ercc1Δ/- liver expression profiles showed preferential extinction of expression of long genes, consistent with genome-wide accumulation of stochastic, transcription-blocking lesions, which affect long genes more than short ones. DR largely prevented this decline of transcriptional output, indicating that DR prolongs genome function. Our findings strengthen the link between DNA damage and aging, establish Ercc1Δ/- mice as powerful model for identifying interventions to promote healthy aging, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and DR-like interventions for preventing neurodegenerative diseases.

2016-09-09 | GSE77321 | GEO

Lifespan extension by diet restriction in DNA repair deficient progeroid Ercc1Δ/- mice [miRNA]

2016-09-09 | GSE77226 | GEO

Increased expression of FOXM1 delays natural and progeroid aging phenotypes

Project description:The FOXM1 member of the forkhead family of transcription factors is known for its pleiotropic C-terminus transcriptional and N-terminus non-transcriptional functions in a wide set of biological processes critical for cellular homeostasis. We previously found that FOXM1 repression during cellular aging accounts for the accrual of senescence phenotypes, which were vastly restored by overexpressing transcriptionally active FOXM1. Here, we found cyclic induction of a N-terminus truncated FOXM1 transgene on progeroid and naturally aged mice, to offset an aging-associated repression of full-length endogenous FoxM1, thereby allowing reinstatement of both transcriptional and non-transcriptional functions. This translated into mitigation of molecular and histopathological progeroid features of progeroid mice, significantly extending its lifespan. Notably, FOXM1 transgene induction also delayed the progressive accumulation of aging phenotypes, while extending the lifespan of naturally aged mice.

2022-01-10 | GSE193147 | GEO

LINE-1 antisense oligonucleotide ameliorate HGPA and WRN aging phenotype.

Project description:Constitutive heterochromatin is responsible for genome repression of DNA enriched in repetitive sequences, telomeres, and centromeres. In higher eukaryotes, constitutive heterochromatin is mostly segregated at the nuclear periphery, where the interaction with the nuclear lamina makes the genome more resistant to transcription. During physiological and pathological premature aging, heterochromatin homeostasis is profoundly compromised. Here we show that LINE-1 (L1) RNA accumulation is an early event in both typical and atypical progeroid syndromes. L1 RNA negatively regulates Suv39H1 enzymatic activity, resulting in heterochromatin loss and onset of senescent phenotypes. Depletion of L1 RNA in cells from different progeroid syndrome patients using specific antisense oligonucleotides (ASO) restores the levels of heterochromatin epigenetic marks, preserves DNA methylation and counteracts the expression of senescence-associated genes. Moreover, systemic delivery of ASO rescues the histophysiology of all tissues and increases the lifespan of Hutchinson-Gilford Progeria Syndrome (HGPS) mouse model. Furthermore, the transcriptional profiling following L1 RNA depletion shows that pathways associated with nuclear chromatin organization, cell proliferation, and transcription regulation were enriched. Similarly, pathways associated with aging, inflammatory response, innate immune response and DNA damage were downregulated. Our results show a key role of L1 RNA in heterochromatin homeostasis in progeroid syndromes and identify a possible therapeutic approach to treat premature aging and related syndromes.

2022-08-24 | GSE198675 | GEO

Increased expression of FOXM1 delays natural and progeroid aging phenotypes

Project description:Increased expression of FOXM1 delays natural and progeroid aging phenotypes

| PRJNA795140 | ENA

Transciptome analysis of TP63 regulated pathways in HNSCC

Project description:Purpose: To identify TP63 expression regulated pathways in HNSCC Methods: A recombinant lentivirus encoding either NS shRNA or TP63 shRNA was introduced into a HNSCC cell line, FaDu. SCCs were gene generated by implanting either FaDu-NS shRNA (n=3) or FaDu-TP63 shRNA into the tongue of athymic nude mice. Tongue SCCs harvested at the end of study were used for transcriptome analysis

2019-03-15 | GSE120689 | GEO

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