Decoding the regulation of a state of 'suspended animation' in killifish

The evolutionary success of life on Earth has been fundamentally shaped by the ability of organisms to adapt to extreme environmental conditions encountered during their lives. Understanding the regulation of these extreme adaptations can reveal conserved resilience pathways with important ramifications for survival across organisms. The African killifish provides a unique vertebrate model to study this question because its embryos naturally enter diapause—a state of suspended animation—that enables survival for years under extreme environmental stress. However, we still lack a fundamental understanding of how this protective state is coordinated across diverse organs and cell types and maintained over prolonged periods.

To uncover the molecular basis of this protective state, we generated a high-resolution, temporally resolved single-cell multi-omic atlas of killifish diapause. We found that despite broad suppression of transcription, cell identity is preserved through stable cell-type-specific chromatin landscapes. Integrating single-cell chromatin accessibility with transcriptional dynamics revealed regulatory networks controlling diapause, with multiple stress-responsive AP-1 family transcription factors emerging as key regulators of the diapause gene regulatory network involved in cellular stress responses and adaptation. These findings establish diapause as a powerful vertebrate model for uncovering mechanisms of cellular resilience and long-term tissue preservation.