The genetic basis of sex differences in murine embryonic stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA601670 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10741300.fastq.gz | Fastqsanger.gz | |||
| SRR10741301.fastq.gz | Fastqsanger.gz | |||
| SRR10741302.fastq.gz | Fastqsanger.gz | |||
| SRR10741303.fastq.gz | Fastqsanger.gz | |||
| SRR10741304.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 89 |
Similar Datasets
Project description:Dosage imbalance of X-chromosomal genes contributes to sex differences, in particular during early development, when both X chromosomes are active in females. X-encoded inhibitors of the differentiation-promoting MAP kinase (MAPK) signalling pathway slow down development, increase levels of naive pluripotency factors and decrease MAPK target gene expression. Through a hierarchical CRISPR screening approach in murine embryonic stem cells (mESC) we have comprehensively identified X-linked genes that modulate MAPK signalling, pluripotency factor expression and differentiation. We show that multiple genes act in concert to drive sex differences in mESC. Dusp9, a known negative regulator of the MAPK pathway alters phosphorylation of MAPK pathway intermediates in female cells, while Klhl13 underlies differences in pluripotency factor expression and differentiation by targeting differentiation-promoting factors for degradation. Klhl13 is a member of the Cullin 3 E3 ubiquitin ligase complex, where it acts as a substrate adaptor to target proteins for proteasomal degradation (Dhanoa et al., 2013). We reasoned that the Klhl13-mediated sex differences we have identified might be due to reduced protein abundance of Klhl13 substrate proteins in female compared to male cells, which affect pluripotency factors, differentiation and MAPK target gene expression. To identify Klhl13 substrates in mESCs, we comprehensively profiled Klhl13 interaction partners and then selected those with increased protein levels in K13-HOM mutant cells. To identify interaction partners, we ectopically expressed either full-length Klhl13 or the substrate-binding Kelch domain, tagged with a green fluorescent protein (GFP), and identified binding partners by Immunoprecipitation-Mass Spectrometry (IP-MS) using a GFP-specific antibody. These experiments were performed in female mESCs with a homozygous Klhl13 deletion. By using this approach, we identify Scml2 and Alg13 as Klhl13 substrates.
2021-03-18 | PXD016729 | Pride
Project description:Dosage imbalance of X-chromosomal genes contributes to sex differences, in particular during early development, when both X chromosomes are active in females. X-encoded inhibitors of the differentiation-promoting MAP kinase (MAPK) signalling pathway slow down development, increase levels of naive pluripotency factors and decrease MAPK target gene expression. Through a hierarchical CRISPR screening approach in murine embryonic stem cells (mESC) we have comprehensively identified X-linked genes that modulate MAPK signalling, pluripotency factor expression and differentiation. We show that multiple genes act in concert to drive sex differences in mESC. Dusp9, a known negative regulator of the MAPK pathway alters phosphorylation of MAPK pathway intermediates in female cells, while Klhl13 underlies differences in pluripotency factor expression and differentiation by targeting differentiation-promoting factors for degradation. Klhl13 is a member of the Cullin 3 E3 ubiquitin ligase complex, where it acts as a substrate adaptor to target proteins for proteasomal degradation (Dhanoa et al., 2013). We reasoned that the Klhl13-mediated sex differences we have identified might be due to reduced protein abundance of Klhl13 substrate proteins in female compared to male cells, which affect pluripotency factors, differentiation and MAPK target gene expression. To identify Klhl13 substrates in mESCs, we comprehensively profiled Klhl13 interaction partners and then selected those with increased protein levels in K13-HOM mutant cells. To identify interaction partners, we ectopically expressed either full-length Klhl13 or the substrate-binding Kelch domain, tagged with a green fluorescent protein (GFP), and identified binding partners by Immunoprecipitation-Mass Spectrometry (IP-MS) using a GFP-specific antibody. These experiments were performed in female mESCs with a homozygous Klhl13 deletion. By using this approach, we identify Scml2 and Alg13 as Klhl13 substrates.
2021-03-18 | PXD017875 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-16 | GSE143784 | GEO
Project description:Kids First Pediatric Research Project on the Genetic Basis of Disorders/Differences of Sex Development (DSD)
| PRJNA335781 | ENA
Project description:Sex differences in RBM20 cardiomyopathy
| PRJNA892331 | ENA
Project description:There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences.
2020-08-05 | GSE155676 | GEO
Project description:Male and female disease states differ in their prevalence, treatment responses, and survival rates. In cardiac disease, women almost uniformly fare far worse than men1-3. Though sex plays a critical role in cardiac disease, the mechanisms underlying sex differences in cardiac homeostasis and disease remain unexplained. Here, we reveal sex-specific cardiac transcriptomes and proteomes and show that cardiac sex differences are predominately controlled via post-transcriptional mechanisms. Using a quantitative proteomics-based approach, we characterize differential sex-specific enriched cardiac proteins, protein complexes, and biological sex processes in the context of global genetic diversity of the Collaborative Cross. We show that differences in cardiac protein expression are established by both hormonal and genetic mechanisms and define two additional pathways, one that is SRY dependent and one that is SRY-independent. We also determined the onset of sex-biased protein expression and discovered that sex disparities in heart tissue occur at the earliest stages of heart development, during the period preceding primary mammalian sex determination. This may explain why congenital heart disease, a leading cause of death whose origin is often developmental, is sex biased. Our results reveal the molecular foundations for the differences in cardiac tissue that underlie sex disparities in health, disease, and treatment outcomes.
2022-08-11 | PXD020139 | Pride
Project description:Sex-related differences in Alzheimer’s disease
| PRJNA839023 | ENA
Project description:The murine pulmonary response is strain specific. Susceptible strains such as C57BL6/J experience an inflammatory response followed by progressive lung disease. Resistant strains such as Balb/c do not experience significant degrees of inflammation or fibrosis. This study aims to determine the genetic basis of sensitivity differences between strains Keywords: other
2003-07-16 | GSE485 | GEO
Project description:In the field, adult male rodents are more frequently infected with hantaviruses than females. Early data suggests that sex steroid hormones modulate sex differences in host immune response. This project focuses on elucidating sex differences in gene expression in the lungs of infected males 15 and 40 days post infection with Seoul virus (naturally occurring hantavirus in Norway rats) relative to infected females 15 and 40 days post infection on 12 RG_U34 GeneChips. Keywords: other
2003-07-16 | GSE488 | GEO