Gonadal sex reversal at single-cell resolution in Znrf3-deficient mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1181816 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31222400_1.fastq.gz | Fastqsanger.gz | |||
| SRR31222400_2.fastq.gz | Fastqsanger.gz | |||
| SRR31222401_1.fastq.gz | Fastqsanger.gz | |||
| SRR31222401_2.fastq.gz | Fastqsanger.gz | |||
| SRR31222402_1.fastq.gz | Fastqsanger.gz |
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Project description:Early gonadal-mesonephros tissues give rise to the developing gonad, with potential to diverge towards either a testis or ovarian gonadal fate. ZNRF3 mutant homozygotic mice develop a variable sex reversal previously uncharacterised at the single cell level. We used scRNA-Seq to compare XX and XY WT C57BL/6J mouse gonads to ZNRF3-deficient mice across multiple timepoints, during and after initial sex determination.
2024-11-29 | GSE280999 | GEO
Project description:Sex differences in the brain as they relate to health and disease are often overlooked in experimental models. Many neurological disorders, like Alzheimer’s disease (AD), multiple sclerosis (MS), and autism, differ in prevalence between males and females. Sex differences originate either from differential gene expression on sex chromosomes or from hormonal differences, either directly or indirectly. To disentangle the relative contributions of genetic sex (XX v. XY) and gonadal sex (ovaries v. testes) to the regulation of hippocampal sex effects, we use the “sex-reversal” Four Core Genotype (FCG) mouse model which uncouples sex chromosome complement from gonadal sex. Transcriptomic and epigenomic analyses of hippocampal RNA and DNA from ∼12 month old FCG mice, reveals differential regulatory effects of sex chromosome content and gonadal sex on X- versus autosome-encoded gene expression and DNA modification patterns. Gene expression and DNA methylation patterns on the X chromosome were driven primarily by sex chromosome content, not gonadal sex. The majority of DNA methylation changes involved hypermethylation in the XX genotypes (as compared to XY) in the CpG context, with the largest differences in CpG islands, promoters, and CTCF binding sites. Autosomal gene expression and DNA modifications demonstrated regulation by sex chromosome complement and gonadal sex. These data demonstrate the importance of sex chromosomes themselves, independent of hormonal status, in regulating hippocampal sex effects. Future studies will need to further interrogate specific CNS cell types, identify the mechanisms by which sex chromosome regulate autosomes, and differentiate organizational from activational hormonal effects.
2022-01-31 | GSE184098 | GEO
Project description:Sex differences in the brain as they relate to health and disease are often overlooked in experimental models. Many neurological disorders, like Alzheimer’s disease (AD), multiple sclerosis (MS), and autism, differ in prevalence between males and females. Sex differences originate either from differential gene expression on sex chromosomes or from hormonal differences, either directly or indirectly. To disentangle the relative contributions of genetic sex (XX v. XY) and gonadal sex (ovaries v. testes) to the regulation of hippocampal sex effects, we use the “sex-reversal” Four Core Genotype (FCG) mouse model which uncouples sex chromosome complement from gonadal sex. Transcriptomic and epigenomic analyses of hippocampal RNA and DNA from ∼12 month old FCG mice, reveals differential regulatory effects of sex chromosome content and gonadal sex on X- versus autosome-encoded gene expression and DNA modification patterns. Gene expression and DNA methylation patterns on the X chromosome were driven primarily by sex chromosome content, not gonadal sex. The majority of DNA methylation changes involved hypermethylation in the XX genotypes (as compared to XY) in the CpG context, with the largest differences in CpG islands, promoters, and CTCF binding sites. Autosomal gene expression and DNA modifications demonstrated regulation by sex chromosome complement and gonadal sex. These data demonstrate the importance of sex chromosomes themselves, independent of hormonal status, in regulating hippocampal sex effects. Future studies will need to further interrogate specific CNS cell types, identify the mechanisms by which sex chromosome regulate autosomes, and differentiate organizational from activational hormonal effects.
2022-01-31 | GSE184013 | GEO
Project description:Purpose: In this study we employed unbiased, genome wide techniques to identify novel enhancers of Sox9 that may cause Disorders of Sex Development (DSDs) when disrupted in the mouse. Methods: We performed ATAC-seq on 60K FACS-purified gonadal cells before and after sex determination to map nucleosome depleted regions (NDRs) indicative of regulatory elements. We then selected 16 putative enhancers present in Sertoli cells. To determine whether these are active enhancers, we performed ChIP-seq for H3K27ac, a histone modification that marks active enhancers. Transient transgenics was performed on select enhancers to determine whether they drive Sertoli-specific expression in vivo. Finally, we selected a single active Sertoli-specific enhancer to delete with CRISPR. Results: We identified a single enhancer upstream of Sox9 that causes complete male-to-female sex reversal in mice when deleted. Conclusions: Our study is the first to identify a single enhacer supstream of Sox9 which drives Sertoli-specific expression in vivo and causes complete male-to-female sex reversal when deleted in the mouse. Furthermore, this enhancer overlaps a region in humans (XY SR) associated to DSDs.
2018-04-12 | GSE99320 | GEO
Project description:Mammalian gonadal sex determination is dependent on proper expression of sex determining genes in fetal gonadal somatic support cells (i.e., pre-granulosa and pre-Sertoli cells in XX and XY gonads, resp.). We used a unique transgenic mouse strain combined with microarray profiling to identify all the differentially expressed transcripts in XX and XY isolated somatic support cells during critical stages of gonadal development and differentiation.
2009-11-09 | GSE18211 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE9504: Expression data from hybrid female Xenopus sex reversal experiment; GSE9505: Expression data from hybrid male Xenopus sex reversal experiment Experiment Overall Design: Refer to individual Series
2008-06-16 | E-GEOD-9507 | biostudies-arrayexpress
Project description:Gonadal sex differentiation – testis versus ovary formation – is a fundamental process required for reproduction and evolution. Reflecting this importance, the embryonic gonads of vertebrate species comprise the same key cell types; germ cells, supporting cells and interstitial steroidogenic cells. Remarkably, the genetic triggers for gonadal sex differentiation vary across species (the SRY gene in mammals, DMRT1 in birds and some turtles, temperature in many reptiles, AMH and various other genes in fishes). Despite this variation, the cell biology of gonadal development was long thought to be largely conserved. Here, we present a comprehensive analysis of gonadal sex differentiation, using the chicken embryo as a model and considering the entire gonad. We sampled over 30,000 cells across several developmental stages, prior, during and after the onset of gonadal sex differentiation. The data provide several new insights into cell lineage specification during vertebrate gonadogenesis. Combining lineage tracing with single cell transcriptomics, the data show that somatic supporting cells of the embryonic chicken gonad do not derive from the coelomic epithelium, in contrast to other vertebrates studied. Instead, the early somatic precursors cells of the gonads in both sexes derive from a DMRT1+/PAX2+/WNT4+/OSR1+ mesenchymal cell population. In particular, PAX2 marks immigrating mesenchymal cells that give rise to the supporting cell lineage. We find a greater complexity of gonadal cell types than previously thought, including the identification of two distinct sub-populations of Sertoli cells in developing testes, and derivation of embryonic steroidogenic cells from a differentiated supporting cell lineage. We provide significantly improved resolution of gonadal cell types and identify several new gonadal marker genes. Altogether, these results indicate that, just as the genetic trigger for sex differs across vertebrate groups, cell lineage specification in the gonad may also vary substantially.
2020-06-03 | GSE143337 | GEO
Project description:To identify markers associated with inherent cellular sex-identity, we analysed cultured macrophages from male and female chick embryos. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages. To determine whether these differences resulted from the actions of gonadal hormones, we induced gonadal sex-reversal to alter the hormonal environment of the developing chick and analysed different tissues and macrophages from male and female embryos.
2014-07-31 | GSE59919 | GEO
Project description:Gonadal trans-differentiation from ovary to testis occurs in a same individual, suggesting a role of epigenetic regulation. However, histone modifications concerning the sex reversal process remain elusive. Here, we report a developmental atlas of histone modifications in the gonadal differentiation, including acetylation, methylation, and ubiquitination, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We provided a detail distribution map of these modification sites including novel histone modifications along histones H2a, H2b, H3, and H4, and revealed their relationship with types of gonadal differentiation. We then determined a testis-enriched histone modification site, H2b monoubiquitination at K120, and its association with spermatogenesis. ChIP-seq demonstrated that the modification was highly enriched in the male sex-determining gene dmrt1, in particular association with its exon regions, suggesting its role in transcriptional elongation of dmrt1 in testis. Together, these data not only provide a new resource for epigenetic study in gonadal development, but also define an association of histone modifications in gonadal differentiation from ovary to testis.
2021-06-30 | GSE168541 | GEO
Project description:Gonadal sex determining (GSD) genes that initiate fetal ovarian and testicular development and differentiation are expressed in the cells of the urogenital ridge that differentiate as somatic support cells (SSCs), i.e., granulosa cells of the ovary and Sertoli cells of the testis. To identify potential new mammalian GSD genes, we analyzed the gene expression differences between XX and XY SSCs cells isolated from the gonads of embryonic day (E) 13 mouse fetuses carrying an EGFP reporter transgene expressed specifically in SSCs. In addition, genome wide expression differences between XX and XY E13 whole gonads were examined. Newly identified differentially expressed transcripts are potential GSD genes involved in unexplained human sex reversal cases. Keywords: microarray, mouse fetal gonadal somatic support cells, sex determination
2006-05-27 | GSE4928 | GEO