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

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). We purified by FACS pre-granulosa and Sertoli cells from mouse fetal gonads and performed bulk RNA-seq and ATAC-seq in triplicates at four developmental stages (E11.5, E12.5, E13.5 and E15.5).