Dynamic Enhancers and 3D Genome Architecture: Orchestrating Stem Cell Fate Decisions

Enhancers play a crucial role in directing gene expression programs essential for cellular differentiation and development. Recent advancements in 3D genome mapping and single-cell analyses have illuminated the significant influence of dynamic enhancer activities and chromatin topology on stem cell fate decisions. Despite these advances, there remain considerable gaps in understanding the precise mechanisms of enhancer-promoter communication, phase separation processes, and metabolic regulation of enhancers. The potential for leveraging enhancer editing for regenerative medicine and disease modeling has yet to be fully realized. This Research Topic seeks to bridge these knowledge gaps by integrating cutting-edge genomics, advanced imaging techniques, and computational methodologies to explore how enhancers and 3D genome architecture influence stem cell behavior. By compiling interdisciplinary research, the aim is to enhance foundational understanding and inspire therapeutic innovations in both stem cell biology and epigenetics.

This Research Topic aims to address multiple key scientific challenges, such as discerning how enhancer dynamics and 3D genome folding regulate stem cell plasticity, investigating how metabolic and environmental factors can modulate enhancer activity to improve cell reprogramming, and understanding how enhancer engineering can be harnessed for disease modeling and regenerative therapies. To achieve these goals, articles utilizing methods like single-cell multi-omics for chromatin mapping, CRISPR-based enhancer editing for functional validation, and assays for phase separation are highly encouraged. With recent innovations such as live imaging of enhancer hubs and AI-enhanced enhancer predictions, this topic aims to provide a roadmap for advancing research in stem cell regulation and genome architecture.

To gather further insights in this domain, we welcome articles addressing, but not limited to, the following themes:

o Enhancer-promoter communication in pluripotency and differentiation.

o Phase separation in enhancer cluster assembly.

o Metabolic regulation of enhancer activity.

o CRISPR-based enhancer engineering for therapeutic applications.

o Non-coding variants and their impact on stem cell dysfunction.

o CTCF/cohesin-mediated topological remodeling in development and disease.

o Enhancer RNAs (eRNAs) as regulators of cell fate.

o Evolutionary conservation of enhancer grammars.

o Environmental cues and epigenetic memory.

o Clinical translation of enhancer-targeting therapies.