• BACH1 directly binds to the Lifr enhancer and recruits STAT3 to drive Lifr transcription, revealing a novel transcriptional mechanism.
• Bach1 knockout attenuates Lifr expression and impairs LIFR-STAT3 signaling, leading to reduced self-renewal of mouse embryonic stem cells.
• Integrated scRNA-seq data show co-upregulation of Bach1 and Lifr in inner cell mass cells, suggesting a role in early embryonic pluripotency.
• This study provides new insights into enhancer regulation and offers potential targets for improving stem cell culture and regenerative medicine.