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Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development

ABSTRACT: Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development

PROVIDER: PRJNA1244148 | ENA |

REPOSITORIES: ENA

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Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development [ATACseq]

Project description:Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development [ATACseq]

| PRJNA1163275 | ENA

Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development [RNA-Seq]

Project description:Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development [RNA-Seq]

| PRJNA1163274 | ENA

Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development

Project description:Gonadal sex determination relies on tipping a delicate balance involving the activation and repression of several transcription factors and signalling pathways. This is likely mediated by numerous non-coding regulatory elements that shape sex-specific transcriptomic programs. To explore the dynamics of these in detail, we performed paired time-series of transcriptomic and chromatin accessibility assays on pre-granulosa and Sertoli cells throughout their development in the embryo, making use of new and existing mouse reporter lines. Regulatory elements were associated with their putative target genes by linkage analysis, and this was complemented and verified experimentally using promoter capture Hi-C. We identified the transcription factor motifs enriched in these regulatory elements along with their occupancy, pinpointing LHX9/EMX2 as potentially critical regulators of ovarian development. Variations in the DNA sequence of these regulatory elements are likely to be responsible for many of the unexplained cases of individuals with Differences of Sex Development.

2025-07-30 | GSE293342 | GEO

Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development [ATACseq]

Project description:Identifying cis-regulatory elements is essential for understanding how gene expression is precisely controlled during critical biological processes like sex determination. In this study, we aimed to uncover the cis-regulatory regions involved in the differentiation of supporting cells as Sertoli cells or pre-granulosa cells in the mouse gonads. To achieve this, we combined ATAC sequencing (ATAC-seq) and Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) of purified supporting cells at four developmental stages in both sexes. ATAC-seq enabled us to capture sexual and temporal changes in gene expression during cell differentiation, while ATAC-seq provided insight into chromatin accessibility, pinpointing regulatory regions that control these expression patterns. By integrating these two datasets, we identified specific cis-regulatory elements that likely guide the fate of supporting cells. Our findings shed light on the complex gene regulatory networks involved in sex fate differentiation, highlighting the critical role of cis-regulatory elements in orchestrating this process. These insights may also have implications for understanding disorders of sexual development (DSDs).

2025-06-01 | GSE277646 | GEO

Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development [RNA-Seq]

Project description:Identifying cis-regulatory elements is essential for understanding how gene expression is precisely controlled during critical biological processes like sex determination. In this study, we aimed to uncover the cis-regulatory regions involved in the differentiation of supporting cells as Sertoli cells or pre-granulosa cells in the mouse gonads. To achieve this, we combined RNA sequencing (RNA-seq) and Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) of purified supporting cells at four developmental stages in both sexes. RNA-seq enabled us to capture sexual and temporal changes in gene expression during cell differentiation, while ATAC-seq provided insight into chromatin accessibility, pinpointing regulatory regions that control these expression patterns. By integrating these two datasets, we identified specific cis-regulatory elements that likely guide the fate of supporting cells. Our findings shed light on the complex gene regulatory networks involved in sex fate differentiation, highlighting the critical role of cis-regulatory elements in orchestrating this process. These insights may also have implications for understanding disorders of sexual development (DSDs).

2025-06-01 | GSE277647 | GEO

FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development

Project description:Forkhead box L2 (FOXL2) is a forkhead box transcription factor expressed in the pituitary, ovaries, and eyelids. Human mutations in FOXL2 associate with the blepharophimosis, ptosis epicanthus and inversus syndrome (BPES), which can be linked to primary ovarian insufficiency, and are indirectly linked with differences of sex development (DSD). Animal studies have shown the crucial role that FOXL2 plays in the development, function, and maintenance of the ovary as well as in sex determination. However, the role of FOXL2 in early human somatic cell ovarian development is largely unknown. In this study, using CRISPR/Cas9 genome activation and a previously published in-house 14-day gonadal differentiation protocol, we show that FOXL2 downregulates coelomic epithelial markers GATA4 and LHX9, female gonadal markers RSPO1 and WNT4, and male gonadal markers SOX9 and NR0B1. Differentially expressed genes were mostly associated with Kyoto encyclopaedia of genes and genomes (KEGG) pathways relating to cell adhesion molecules and gene ontology (GO) pathways relating to extracellular matrix and junction formation. Moreover, comparative analysis with existing single cell RNA sequencing data from human in vivo-derived data elucidated that FOXL2 initiates downregulation of coelomic epithelial genes GATA4, LHX9 and UPK3B at day 6. At day 8, the genes ARX and GATA2 are transiently upregulated by FOXL2 induction and then downregulated as the genes LGR5, TSPAN8, OSR1 and TAC1 become upregulated. Thus, FOXL2 seems to support the exit of the differentiating cells from coelomic epithelium and first drives the cells towards a transitional identity and then into early supporting gonadal-like cells. The findings of this study will help largely in understanding normal gonadal development which can be used as a basis to elucidate pathological gonadal development underlying BPES.

2025-03-26 | GSE282662 | GEO

Gonadal supporting cells acquire sex-specific regulatory elements during mammalian sex determination

Project description:Gonadal supporting cells acquire sex-specific regulatory elements during mammalian sex determination

| PRJNA486735 | ENA

FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development

Project description:FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development

| PRJNA1189561 | ENA

Supporting-like cells are an alternative gonadal steroidogenic lineage that is conserved in amniotes

Project description:In mammals, the production of sex hormones is widely considered to depend on the interstitial lineage of the gonad, which differentiates into Leydig cells in males or theca cells in females. However, certain mammalian species evidence gonadal steroidogenic activity prior to the specialization of these interstitial lineages, suggesting that alternative cell types may assume this function. Here, using single-cell RNA-seq of rabbits developing gonads, we reveal a previously unrecognized role for supporting-like cells (SLCs), which can act as a major steroidogenic lineage during mammalian embryonic development.

2026-06-30 | GSE331375 | GEO

Supporting-like cells are an alternative gonadal steroidogenic lineage that is conserved in amniotes

Project description:Supporting-like cells are an alternative gonadal steroidogenic lineage that is conserved in amniotes

| PRJNA1467978 | ENA