Functional robustness of spermatogonial stem cells after induction of hyperactive Hras
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA531490 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8867430_1.fastq.gz | Fastqsanger.gz | |||
| SRR8867430_2.fastq.gz | Fastqsanger.gz | |||
| SRR8867432_1.fastq.gz | Fastqsanger.gz | |||
| SRR8867432_2.fastq.gz | Fastqsanger.gz | |||
| SRR8867433_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:We report on gene expression in stem cell-enriched, undifferentiated spermatogonia isolated from the adult mouse testis, in which one group are wild type and the other group contain a heterozygous Hras G12V mutation.
2019-04-18 | GSE129493 | GEO
Project description:Accumulating evidence indicates that paternal age correlates with disease risk in children. De novo gain-of-function mutations in the FGF-RAS-MAPK signaling pathway are known to cause a subset of genetic diseases associated with advanced paternal age, such as Apert syndrome, achondroplasia, Noonan syndrome, and Costello syndrome. It has been hypothesized that adult spermatogonial stem cells with pathogenic mutations are clonally expanded over time and propagate the mutations to offspring. However, no model system exists to interrogate mammalian germline stem cell competition in vivo. In this study, we created a lineage tracing system, which enabled undifferentiated spermatogonia with endogenous expression of HrasG12V, a known pathogenic gain-of-function mutation in RAS-MAPK signaling, to compete with their wild-type counterparts in the mouse testis. Over a year of fate analysis, neither HrasG12V-positive germ cells nor sperm exhibited a significant expansion compared to wild-type neighbors. Short-term stem cell capacity as measured by transplantation analysis was also comparable between wild-type and mutant groups. Furthermore, although constitutively active HRAS was detectable in the mutant cell lines, they did not exhibit a proliferative advantage or an enhanced response to agonist-evoked pERK signaling. These in vivo and in vitro results suggest that mouse spermatogonial stem cells are functionally resistant to a heterozygous HrasG12V mutation in the endogenous locus and that mechanisms could exist to prevent such harmful mutations from being expanded and transmitted to the next generation.
| S-EPMC6519842 | biostudies-literature
Project description:Oncogenic activating mutations in Ras genes are among the most common drivers of human disease. Treating mouse skin with the chemical carcinogen DMBA induces a characteristic mutation in Hras at codon 61. To understand how skin responds to a constitutive lack of Hras, we generated a cohort of Hras knockout mice.
2015-03-01 | GSE60769 | GEO
Project description:Oncogenic activating mutations in Ras genes are among the most common drivers of human disease. Treating mouse skin with the chemical carcinogen DMBA induces a characteristic mutation in Hras at codon 61. To understand how skin responds to a constitutive lack of Hras, we generated a cohort of Hras knockout mice. A backcross was generated using male Mus spretus and female FVB/N Hras-/- mice; female F1 hybrids were mated with male FVB/N Hras -/- or Hras -/+ mice to generate a backcross population. This series contains mice that were Hras -/-. Mice were aged to 8 weeks and a tail skin sample was snap frozen.
2015-03-01 | E-GEOD-60769 | biostudies-arrayexpress
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-08 | PXD012506 | Pride
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-08 | PXD012505 | Pride
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-12 | E-MTAB-7672 | biostudies-arrayexpress
Project description:To functionally determine the effect of m6A-regulated HRAS, we specifically demethylated the m6A of HRAS using dm6ACRISPR system, fusing the catalytically dead Type VI-B Cas13 enzyme with the m6A demethylase FTO (dCas13b-FTO).The dCas13b-FTO combined with HRAS-gRNA or gRNA-control were transfected into bladder cancer 5637 cells, and then subjected to RNA-sequencing analysis.
2022-08-27 | GSE211698 | GEO
Project description:In vitro and in vivo aging of mouse spermatogonial stem cells alters stem cell function based on quantitative spermatogonial stem cell transplantation analyses. We used microarrays to identify differential gene expression in vitro and in vivo aged spermatogonial stem cells to identify potential causes of observed phenotypic differences in aged spermatogonial stem cell function. Spermatogonial stem cells were isolated from young and serial-transplanted aged mouse donors and cultured for short and long periods. Spermatogonial stem cells were isolated from cultures and subjected to microarray analysis to identify differential gene expression.
2011-02-04 | E-GEOD-27043 | biostudies-arrayexpress
Project description:Silencing of gene expression by methylation of CpG islands in regulatory elements is frequently observed in cancer. However, an influence of the most common oncogenic signalling pathways onto DNA methylation has not yet been investigated thoroughly. To address this issue, we identified genes suppressed in HRAS-transformed rat fibroblasts but up-regulated after treatment with the demethylating agent 5-Aza-CdR and with the MEK1,2 inhibitor U0126. Analysis of gene expression by microarray and Northern blot analysis revealed the MEK/ERK target genes clusterin, Mmp2, Ppicap, syndecan 4, Timp2, Thbs1 to be repressed in the HRAS-transformed FE-8 cells in a MEK/ERK- and in a methylation-dependent manner. Hypermethylation of putative regulatory elements in HRAS-transformed cells as compared to immortalized fibroblasts was detected within a CpG island 14.5 kb upstream of clusterin, within the clusterin promoter and within a CpG island of the Mmp2 promoter by bisulphite sequencing. Furthermore, hypermethylation of the clusterin promoter was observed ten days after induction of HRAS in immortalized rat fibroblasts and a clear correlation between reduced clusterin expression and hypermethlyation could also be observed in distinct rat tissues. These results suggest that silencing of individual genes by DNA methylation is controlled by oncogenic signalling pathways, yet the mechanisms responsible for initial target gene suppression are variable. Experiment Overall Design: Gene expression was analyzed in immortal (208F) and HRAS oncogene-transformed (FE8) rat fibroblasts after demethylation by 5-aza-2'-deoxycytidine. Genes potentially methylated in RAS-transformed cells were identified by bisulphite sequencing
2007-11-06 | E-GEOD-4427 | biostudies-arrayexpress