PLX236394

GSE110215: Gender-Specific Regulatory Landscapes in Pluripotency and Reprogramming

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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