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.
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)
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.
Project description: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.
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.
Project description:To study the impact of SF3B1 mutations on alternative splicing and the effect of H3B-8800 splicing modulator in wild type and SF3B1-mutant chronic lymphocytic leukemia cells, we established SF3B1 K700E MEC1 CLL isogenic cell line and carried out RNA deep sequencing in SF3B1 wild type and K700E MEC1 cell lines upon H3B-8800 treatment.
Project description:CUG-BP, Elav-like family (CELF) proteins regulate alternative splicing. In MHC-CELFdelta transgenic mice, CELF-mediated alternative splicing is disrupted in heart muscle via expression of a nuclear dominant negative CELF protein under an alpha-myosin heavy chain promoter. MHC-CELFdelta mice develop dilated cardiomyopathy and contractile dysfunction by 3 weeks of age, shortly after the transgene is activated and splicing defects appear. Cardiac function and heart size spontaneously recover with age in a low-expressing (mild) line of MHC-CELFdelta mice despite persistence of dominant negative protein expression and splicing defects, whereas there is no recovery in a higher-expressing (severe) line that also experiences early muscle death and fibrosis. In this study, we explored the basis for this functional recovery by comparing the gene expression profiles in the hearts of low- and high-expressing lines of MHC-CELFdelta mice to those of wild type littermates at 3 weeks (when cardiac dysfunction is maximal) and 24 weeks (when the low-expressing line has recovered) using microarrays. We found that differences in gene expression are greatly reduced in older animals from the low-expressing line, but were exacerbated in the high-expressing line. We did not find evidence of a new compensatory pathway being activated in the low-expressing line with age, and propose that recovery may occur due to developmental stage-specific compatibility of CELF-dependent splice variants with the changing cellular environment of cardiomyocytes. Microarray analysis was performed on total RNA extracted from whole hearts of female mice: three MHC-CELFdelta-10 (high-expressing line) and three MHC-CELFdelta-574 (low-expressing line) were collected at 3 weeks, and five MHC-CELFdelta-10 and five MHC-CELFdelta-574 were collected at 24 weeks. Two wild type mice from each line were collected at each time point (n = 4 total wild type at 3 weeks, and n = 4 total wild type at 24 weeks).
Project description:We sequenced mRNA from E18.5 mouse cortex (3 wild-type vs 3 Nova2-/- and 3 wild-type vs 3 Nova1-/-) and from E18.5 mouse mid- and hind-brain (3 wild-type vs 3 Nova1-/-) to compare gene expression level and alternative splicing events between wild-type and Nova mutant mice.