Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [ChIP]

ABSTRACT: Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [ChIP]

PROVIDER: PRJNA1020775 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [ChIP]

Project description:Sexual dimorphism in kidney injury markers, such as Klotho, is frequently underestimated or disregarded, as most of the preclinical research is done in male animals. Klotho is well-linked to renal health and its deletion in mice results in a severe accelerated aging-like phenotype and premature death. Here, we identified candidate Klotho enhancers and discovered their function using mice carrying deletions in the enhancer loci. Candidate Klotho enhancers were deleted using CRISPR/Cas9 genome editing. Warm ischemia-reperfusion surgery (IRI) was performed bilaterally to induce acute kidney injury and unilaterally in a fibrosis model. Using ChIP-seq and RNA-seq, we analyzed renal chromatin features and gene expression. ELISA and colorimetric assays were used to measure serum FGF23 and serum component levels. Removal of the enhancer caused more substantial reduction in Klotho mRNA levels in female mice compared to males (90 vs. 50%), supported by gene promoter marks remaining more pronounced in males. Weight, lifespan, and fertility of mice lacking the enhancers were not impacted. Only male mutant mice displayed higher Havcr1 expression after IRI than controls (mean 1048 vs. 231.4, p=0.0016). 28 days after unilateral IRI, only males displayed increased fibrosis markers, but with no difference between genotypes. Our findings reveal sexual dimorphism of Klotho gene expression and its enhancer regulation. Only male mutant mice were more susceptible to acute injury and the enhancer deletion had no impact on fibrosis. Additional investigation into the mechanisms governing Klotho regulation is imperative to reassess its effectiveness as a kidney injury marker.

2024-04-04 | GSE243944 | GEO

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp1]

2024-04-04 | GSE243945 | GEO

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp2]

2024-04-04 | GSE255885 | GEO

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury

Project description:Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury

| PRJNA1020768 | ENA

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp1]

Project description:Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp1]

| PRJNA1020778 | ENA

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp2]

Project description:Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp2]

| PRJNA1076918 | ENA

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-04 | GSE243946 | GEO

Sexual dimorphism in mice

Project description:Sexual dimorphism in mice

| PRJEB2572 | ENA

Sexual dimorphism in early osteoclasts demonstrates enhanced inflammatory pathway activation in female cells

Project description:Sexual dimorphism of the skeleton is well documented. At maturity, the male skeleton is typically larger and has a higher bone density than the female skeleton. However, the underlying mechanisms for these differences are not completely understood. In this study, we examined sexual dimorphism in the formation of osteoclasts between cells from female and male mice. We found that the number of osteoclasts in bones was greater in females. Similarly, in vitro osteoclast differentiation was accelerated in female osteoclast precursor (OCP) cells. To further characterize sex differences between female and male osteoclasts, we performed gene expression profiling of cultured, highly purified, murine bone marrow OCPs that had been treated for 3 days with M-CSF and RANKL. We found that 125 genes were differentially regulated in a sex-dependent manner. In addition to genes that are contained on sex chromosomes, transcriptional sexual dimorphism was found to be mediated by genes involved in innate immune and inflammatory response pathways. Furthermore, the NFκB-NFATc1 axis was activated earlier in female early osteoclasts, which partially explains the differences in transcriptomic sexual-dimorphism in these cells. Collectively, these findings identify a sex-dependent intrinsic difference in early osteoclasts, which results from an altered response to osteoclastogenic stimulation. In humans these differences could contribute to the lower peak bone mass and increased risk of osteoporosis that females demonstrate relative to males.

2021-05-14 | GSE153299 | GEO

Sexual dimorphism in osteogenic differentiation

Project description:Sexual dimorphism in osteogenic differentiation

| PRJNA768873 | ENA