Pluto Bioinformatics

GSE110215: Gender-Specific Regulatory Landscapes in Pluripotency and Reprogramming

Bulk RNA sequencing

How gender influences the molecular properties of pluripotent stem cells (PSCs) remains incompletely understood. The reprogramming of somatic cells to pluripotency induces reactivation of the silent X chromosome. Here, we address the mechanisms by which gender modulates pluripotency by characterizing the transcriptional, genetic and pluripotency exit states of isogenic male and female mouse induced PSCs (iPSCs). We find that gender-specific differences arise as a result of reprogramming and are mostly resolved upon culture as concomitant with X chromosome loss. Female-like exit of pluripotency is compatible with global DNA methylation in female XX ESCs with reduced Dusp9 dosage. Epigenomic profiling revealed that ESCs possess gender-specific chromatin accessibility landscapes associated with pluripotency and development that correlate with accessibility of key pluripotency and signaling transcription factor binding sites, including KLF/ESRRB/OCT4/SOX2 and AP-1/TEAD. The differential binding sites enrichment in gender-specific open chromatin regions provides a molecular link between these regulators, pluripotency stabilization and exit from pluripotency. We also show that XY ESCs proliferate at a higher rate than XX ESCs irrespective of culture conditions. Our results uncover new molecular insights on gender differences in PSCs and highlight the importance of chromatin in mediating gender-specific cellular states. SOURCE: Vincent Pasque (vincent.pasque@kuleuven.be) - KU Leuven