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Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217703 | GEO | 2023/12/31

REPOSITORIES: GEO

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Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [Hi-C]

Project description:Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in ageing and are targets of DNA damage and DNA damage response. Although short telomeres have been implicated in heart failure, little is known about the role of telomeres in cardiomyocytes.To fill this gap in knowledge, we studied myocardial ageing in the form of telomere lengths under isogenic background.

2023-12-31 | GSE217702 | GEO

Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [CUT&Tag]

2023-12-31 | GSE230455 | GEO

Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [RNA-Seq]

2023-12-31 | GSE217701 | GEO

Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes

Project description:Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes

| PRJNA900183 | ENA

Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [CUT&Tag]

Project description:Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [CUT&Tag]

| PRJNA961155 | ENA

Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [Hi-C]

Project description:Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [Hi-C]

| PRJNA900186 | ENA

Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [RNA-Seq]

Project description:Investigating the role of telomere length in 3D spatiotemporal gene regulation in cardiomyocytes [RNA-Seq]

| PRJNA900187 | ENA

Telomere Length Regulation

Project description:The number of (TTAGGG)n repeats at the ends of chromosomes is highly variable between individual chromosomes, between different cells and between species. Progressive loss of telomere repeats limits the proliferation of pre-malignant human cells but also contributes to aging by inducing apoptosis and senescence in normal cells. Despite enormous progress in understanding distinct pathways that result in loss and gain of telomeric DNA in different cell types, many questions remain. Further studies are needed to delineate the role of damage to telomeric DNA, replication errors, chromatin structure, liquid-liquid phase transition, telomeric transcripts (TERRA) and secondary DNA structures such as guanine quadruplex structures, R-loops and T-loops in inducing gains and losses of telomere repeats in different cell types. Limitations of current telomere length measurements techniques and differences in telomere biology between species and different cell types complicate generalizations about the role of telomeres in aging and cancer. Here some of the factors regulating the telomere length in embryonic and adult cells in mammals are discussed from a mechanistic and evolutionary perspective.

| S-EPMC9289283 | biostudies-literature

Spatiotemporal regulation of GLI target genes in the mammalian limb bud

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-07-01 | E-GEOD-58222 | biostudies-arrayexpress

Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling.

Project description:AimsTelomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFβ) signalling pathway where inhibiting TGFβ signalling maintains telomere length. The relationship between Pim1 and TGFβ has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFβ signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.Methods and resultsTelomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGFβ signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGFβ signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGFβ pathway genes.ConclusionPim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGFβ pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.

| S-EPMC7797214 | biostudies-literature

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