Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

ABSTRACT: Alternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome-wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus and white adipose tissue from wild-type C57BL6/J male mice (4 and 18-months-old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone and white adipose tissue between the different age groups (ranging from 27-246 AS genes corresponding to 0.3-3.2% of the total number of genes analyzed). For skin, skeletal muscle and bone we included a later age group (28-month-old) that showed the number of alternatively spliced genes increased with age in all three tissues (P<0.01). Analysis of alternatively spliced genes across all tissues by gene-ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson-Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with impaired developmental splicing. As progerin accumulates the number of genes with AS increases compared to in wild-type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known.

ORGANISM(S): Mus musculus

PROVIDER: GSE74274 | GEO | 2015/11/30

SECONDARY ACCESSION(S): PRJNA299629

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The effect of age on alternative splicing in different tissues of wild-type mice

Project description:Exon level expression analysis for the physiological aging study data set to analyze the effect of age on alternative splicing in different tissues and age groups of wild-type mice Analysis of the effect of age on alternative splicing (AS) using exon microarrays to interrogate the differential exon usage of the entire genome of aging wild-type male C57BL/6J mice (4- and 18-month-old) in five tissues (skin, skeletal muscle, bone, thymus, and white adipose tissue) and in an additional 28-month-old age group, which allowed for age-related AS analysis of the skin, skeletal muscle and bone tissues. We found AS genes with age in all tissue, we show that the number of AS genes increased with age and that AS genes across all tissues are involved in RNA processing. Note: This dataset is one of the 2 datasets in the overall study. An additional data set series is available with exon expression analysis of HGPS mice to analyze the effect of progerin expression on alternative splicing. The two datasets are linked together in the SuperSeries GSE67289. A link to the SuperSeries is available at the bottom of this page. 65 tissue samples from wild-type male C57BL/6J mice; from 5 different tissues (ventral skin, skeletal muscle, bone, muscle, and white adipose tissue) and from 3 different age groups: 4, 18 and 28 months (for skin skeletal muscle and bone ) and from 2 different age groups: 4 and 18 months (for ventral skin, skeletal muscle, bone, thymus and white adipose tissue)

2015-11-01 | E-GEOD-67287 | biostudies-arrayexpress

The effect of age on alternative splicing in different tissues of wild-type mice

2015-11-01 | GSE67287 | GEO

The effect of progerin expression on alternative splicing in keratinocytes of HGPS mice

Project description:Exon level expression analysis for the HGPS pathological aging study data set to analyze the effect of progerin expression on alternative splicing in keratinocytes of HGPS mice. Analysis of the effect of pathological aging (transgenic progerin expression) on alternative splicing (AS) using exon microarrays to interrogate the differential exon usage of the entire genome of HGPS mice (postnatal day 24 and 35) and their wild-type litter mates. Our results suggests that early expression of progerin impairs developmental splicing but that as progerin accumulates, the number of genes with AS increases, similar to what is observed in aging wild-type mice. This dataset is one of the 2 datasets in the overall study. An additional data set series is available with exon expression analysis of aging wild-type mice to analyze the effect of age on alternative splicing during physiological aging. The two datasets are linked together in the SuperSeries GSE67289. A link to the SuperSeries is available at the bottom of this page. 16 skin keratinocyte samples from 2 different age groups: postnatal day 24 and postnatal day 35, from 8 HGPS samples and 8 genotype negative (wild-type) littermates.

2015-11-01 | E-GEOD-67288 | biostudies-arrayexpress

The effect of progerin expression on alternative splicing in keratinocytes of HGPS mice

2015-11-01 | GSE67288 | GEO

Mus musculus

Project description:Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

| PRJNA299629 | ENA

Progerin-induced changes in gene expression

Project description:The premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A1. Progerin is also sporadically expressed in wild type cells and has been linked to physiological aging. HGPS cells exhibit extensive nuclear defects including abnormal chromatin structure and increased DNA damage. At the organismal level, HGPS affects several tissues particularly of mesenchymal origin. How the cellular defects of HGPS cells lead to the organismal defects has been unclear. To begin to unravel how progerin leads to disease phenotypes, we analyzed time-dependent changes in transcriptional profiles in response to progerin expression in a hTERT-immortalized skin fibroblast cell line expressing either GFP-progerin or the GFP-wt lamin A control Keywords: time course, cell line comparison

2008-02-09 | GSE10123 | GEO

The Heterochromatin protein 1 is a master regulator in RNA splicing precision deficient in ulcerative colitis

Project description:Defects in RNA splicing have been linked to numerous human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that, in the gut epithelium of patients with ulcerative colitis (UC), the expression of the chromatin and alternative splicing regulator HP1g is strongly reduced. Accordingly, inactivation of the HP1g gene in the mouse gut triggered several IBD-like traits, including inflammation and dysbiosis. In parallel, we discovered that its loss of function broadly increased splicing noise, reducing requirement for canonical splicing consensus sequences, and favoring the usage of cryptic splice sites at numerous genes with key functions in gut biology. This notably resulted in the production of progerin, a noncanonical toxic splice variant of prelamin A mRNA, responsible for the Hutchinson Gilford Progeria Syndrome (HGPS) of premature aging. Likewise, production of progerin transcript was found to be a signature of colonic cells from UC patients. Thus, our study identifies HP1g as a regulator of RNA metabolism in vivo, providing a unique mechanism linking anti-inflammation and accuracy of RNA splicing in the gut epithelium. HP1 defect may confer a general disturbance in RNA splicing precision to scrutinize in IBD and more generally in accelerating aging diseases.

2022-10-25 | PXD031580 | Pride

Defining the age-dependent and tissue-specific circadian transcriptome in male mice

Project description:Cellular circadian clocks direct a daily transcriptional program that supports homeostasis. Emerging evidence supports age-associated changes in circadian functions. To define age-dependent changes at the systems level, we profiled the circadian transcriptome in the hypothalamus, lung, heart, kidney, skeletal muscle, and adrenal gland in 3 age groups. We found age-dependent and tissue-specific clock output changes. Aging reduced the number of rhythmically expressed genes (REGs), indicative of weakened circadian control. Many genes gained rhythmicity in old tissues, reflecting an adaptive response. REGs were enriched for the hallmarks of aging, adding a new dimension to understanding aging. Differential gene expression analysis found that there were temporally distinct clusters of genes in tissue-specific manner. This novel analysis extends the landscape of the understanding of aging. Increased daily gene expression variability is a common feature of aged tissues. Our data highlight the impact of aging on circadian function and temporal changes in gene expression.

2023-01-10 | GSE201207 | GEO

Transcriptional profiling of liver samples from Lmna Gly609Gly knock-in mice

Project description:Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. We report herein a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. By using this animal model, we have developed an antisense morpholino–based therapy that prevents the pathogenic Lmna splicing, dramatically reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotide–based therapies for treating human diseases of accelerated aging. 6 samples, three from LmnaG609G/G609G mice and three from control Lmna+/+ mice

2012-01-13 | E-GEOD-32609 | biostudies-arrayexpress

Expression profiling of 3 and 24 months mouse skeletal muscle (RNA-seq)

Project description:Aging in multicellular organisms is characterized by gradual decline of organ functionality. To study the aging process, we used mRNA sequencing (mRNA-seq) to identify gene expression changes during aging in healthy mice. Skeletal muscle tissues of wild-type mice at 3 months and 24 months of age were collected and mRNA-seq libraries were prepared and sequenced on a HiSeq2500 by single-end sequencing with 100 bp read length. Analysis of the expression profiles of aged skeletal muscle tissues showed decreased mRNA levels of genes function in lipid metabolism, peptidase activity and response to stimulus.

2018-11-03 | E-MTAB-5176 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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