Dissecting gonadal cell lineage specification and sex determination during human development using a single-cell transcriptomics approach
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA678278 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gonadal somatic cells are the main players in gonad development and are important for sex determination and germ cell development. Here, using a time-series scRNA-seq strategy, we analyzed the fetal germ cells (FGCs) and gonadal somatic cells in human embryos and fetuses. Clustering analysis of testes and ovaries revealed several novel cell subsets, including POU5F1+SPARC+ FGCs and KRT19+ somatic cells. Furthermore, our data indicated that DLK1+ cells may be the progenitors of steroidogenic cell lineages in both sexes and that TAC1+ cells may be the progenitors of granulosa cells in females. Intriguingly, the testosterone synthesis function transitioned from fetal Sertoli cells to adult Leydig cells in a step-wise manner. Moreover, interactions between gonadal somatic cells were systematically explored and verified in our study. In detail, we observed that Sertoli cells interacted with Leydig cells through DHH-PTCH1 and PDGFA-PDGFRA/PDGFRB ligand-receptor gene pairs. More importantly, we identified cell type-specific developmental defects of both FGCs and gonadal somatic cells in a Turner syndrome embryo (45, XO). Our work provides a blueprint of the complex yet highly ordered development and interactions of human FGCs and gonadal microenvironment cells.
2022-12-31 | GSE161421 | GEO
Project description:Gonadal somatic cells are the main players in gonad development and are important for sex determination and germ cell development. Here, using a time-series single-cell RNA sequencing (scRNA-seq) strategy, we analyzed fetal germ cells (FGCs) and gonadal somatic cells in human embryos and fetuses. Clustering analysis of testes and ovaries revealed several novel cell subsets, including POU5F1+SPARC+ FGCs and KRT19+ somatic cells. Furthermore, our data indicated that the bone morphogenetic protein (BMP) signaling pathway plays cell type-specific and developmental stage-specific roles in testis development and promotes the gonocyte-to-spermatogonium transition (GST) in late-stage testicular mitotic arrest FGCs. Intriguingly, testosterone synthesis function transitioned from fetal Sertoli cells to adult Leydig cells in a stepwise manner. In our study, potential interactions between gonadal somatic cells were systematically explored and we identified cell type-specific developmental defects in both FGCs and gonadal somatic cells in a Turner syndrome embryo (45, XO). Our work provides a blueprint of the complex yet highly ordered development of and the interactions among human FGCs and gonadal somatic cells.
| S-EPMC9684167 | biostudies-literature
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:Gonadal sex determination represents a unique model for studying cell fate decisions. However, a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. Here, we investigated the origin, specification, and subsequent sex-specific differentiation of a previously uncharacterized population of supporting-like cells (SLCs) in the developing mouse gonads. The SLC lineage is closely related to the coelomic epithelium and specified as early as E10.5, making it the first somatic lineage to be specified in the bipotential gonad. SLC progenitors are localized within the genital ridge at the interface with the mesonephros and initially coexpress Wnt4 and Sox9. SLCs become sexually dimorphic around E12.5, progressively acquire a more Sertoli- or pregranulosa-like identity and contribute to the formation of the rete testis and rete ovarii. Last, we found that WNT4 is a crucial regulator of the SLC lineage and is required for normal development of the rete testis. In the present study, we built a transcriptomic atlas of the entire cell population of the developing female and male gonads during the process of mouse sex determination. We identified a previously uncharacterized population of supporting-like cells (SLC) and shed light on the origin and the developmental trajectory of this important cell lineage during the process of testis and ovary development.
2022-05-27 | GSE184708 | GEO
Project description:A critical transcription factor required for mammalian male sex determination is SRY (sex determining region on the Y chromosome). The expression of SRY in precursor Sertoli cells is one of the initial events in testis development. The current study was designed to determine the impact of environmentally induced epigenetic transgenerational inheritance on SRY during gonadal sex determination in the male. The agricultural fungicide vinclozolin and vehicle control (DMSO) exposed gestating females (F0 generation) during gonadal sex determination promoted the transgenerational inheritance of differential DNA methylation in sperm of the F3 generation (great grand-offspring). The fetal gonads in F3 generation males were used to identify potential alterations in SRY binding sites in the developing Sertoli cells. Chromatin immunoprecipitation with an SRY antibody followed by genome-wide promoter tiling array (ChIP-Chip) was used to identify alterations in SRY binding. A total of 81 adjacent oligonucleotide sites and 173 single oligo SRY binding sites were identified to be altered transgenerationally in the Sertoli cell vinclozolin lineage F3 generation males. Observations demonstrate the majority of the previously identified normal SRY binding sites were not altered and the altered SRY binding sites were novel and new additional sites. The chromosomal locations, gene associations and potentially modified cellular pathways were investigated. In summary, environmentally induces epigenetic transgenerational inheritance of germline epimutations appears to alter the cellular differentiation and development of the precursor Sertoli cell SRY binding during gonadal sex determination that influence the developmental origins of adult onset testis disease.
2015-08-28 | GSE72469 | GEO
Project description:Single Cell transcriptomic atlas of mouse sex determination and gonadal differentiation
| PRJNA765715 | ENA
Project description:Purpose: In this study we employed unbiased, genome-wide techniques to identify regulatory elements during murine sex determination. Methods: We performed ATAC-seq on 60K FACS-purified XX and XY gonadal cells before and after sex determination to map nucleosome depleted regions (NDRs) indicative of regulatory elements. To determine whether these are active enhancers, we performed ChIP-seq for H3K27ac, a histone modification that marks active enhancers in both sexes and time points. Transient transgenics was performed on select enhancers to determine whether they are functional in gonads during the sex determination stage. Results: We have produced a genome wide map of potential regulatory elements and active enhancers during the process of murine sex determination. Furthermore, we validated the power of our dataset by identifying a novel enhancer downstream of Bmp2, a female-specific gene. Conclusions: This work supplies a powerful resource for identifying chromatin regulatory elements active during mammalian sex determination.
2019-01-02 | GSE118755 | GEO
Project description:Embryonic day 13 (E13), E14, and E16 rat testes and ovaries were used for microarray analysis, as well as E13 testis organ cultures that undergo testis morphogenesis and develop seminiferous cords in vitro. A list of 109 genes resulted from a selective analysis for genes present in male gonadal development and with a 1.5-fold change in expression between E13 and E16. Characterization of these 109 genes potentially important for testis development revealed that cytoskeletal-associated proteins, extracellular matrix factors, and signaling factors were highly represented. Throughout the developmental period (E13-E16), sex-enriched transcripts were more prevalent in the male with 34 of the 109 genes having testis-enriched expression during sex determination. In ovaries, the total number of transcripts with a 1.5-fold change in expression between E13 and E16 was similar to the testis, but none of those genes were both ovary enriched and regulated during the developmental period. Genes conserved in sex determination were identified by comparing changing transcripts in the rat analysis herein, to transcripts altered in previously published mouse studies of gonadal sex determination. A comparison of changing mouse and rat transcripts identified 43 genes with species conservation in sex determination and testis development. Profiles of gene expression during E13-E16 rat testis and ovary development are presented and candidate genes for involvement in sex determination and testis differentiation are identified. Analysis of cellular pathways did not reveal any specific pathways involving multiple candidate genes. However, the genes and gene network identified influence numerous cellular processes with cellular differentiation, proliferation, focal contact, RNA localization, and development being predominant. Keywords: expression analysis, testis, ovary, sex determination
2008-02-20 | GSE10558 | 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. Experiment Overall Design: XX and XY somatic support cells (SSC) were isolated by flow cytometry from embryonic day (E) 11.5 and E12.5 mouse gonads. Total RNA was isolated from pools of isolated cells; 3 pools per sex and each timepoint.
2009-11-13 | E-GEOD-18211 | biostudies-arrayexpress
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