Fosl2 orchestrates chromatin accessibility to determine granulosa cells developmental trajectories [scRNA-Seq]

ABSTRACT: Granulosa cells (GCs) behave as the most dynamically responsive cell lineage to encourage continuous ovarian folliculogenesis; however, the determinants of their developmental trajectories and interplay with downstream transcription circuitry remain poorly understood. In this research, we delineate the genome-wide redistribution of accessible chromatin regions that drive broad developmental-related transcriptomic changes aacross porcine and murine follicular stages. We report the distinct GCs-activated accessibility regions (GAAs), are responsible for augmenting of flanking GCs-involved developmental genes (GDGs) expression, serving as a key requirement for transcription in response to developmental cues. Mechanistically, the transcription factor Fosl2 is robustly recruited to GAAs, facilitating chromatin accessibility state transition. The enlarged GAAs signal driven by Fosl2 loading subsequently induces a significant upregulation of adjacent GDG expression. Additionally, the germ cell-specific deletion of Fols2 induces perturbations in GCs cellularity, which consequently precipitate endocrine dysfunction and a progressive deterioration in reproductive competence in murine models. Together, our research provides a detailed depiction of the dynamic chromatin accessibility landscape throughout the developmental continuum of GCs, revealing the indispensable function of Fosl2 in controlling the transcriptional activation via the reconfiguration of the widespread chromatin state.

ORGANISM(S): Mus musculus

PROVIDER: GSE281100 | GEO | 2024/11/10

REPOSITORIES: GEO