The hidden weavers: A review of DNA/RNA R-loops in stem cell biology and therapeutic potential

R-loops, three-stranded nucleic acid structures composed of RNA-DNA hybrids, are increasingly recognized as central regulators of genomic stability and transcription. These structures play critical roles across various cellular processes, including DNA replication, repair, and gene regulation, with significant implications for stem cell biology and disease pathogenesis. This review comprehensively explores the molecular underpinnings of R-loop formation, emphasizing the dual nature of R-loops in both facilitating normal cellular functions and contributing to genomic instability. We critically evaluate the current methodologies for R-loop detection, highlighting the need for more precise and higher-resolution techniques to enhance our understanding of R-loop dynamics and their biological consequences. Importantly, the review provides novel insights into the pivotal role of R-loops in stem cell biology, suggesting that manipulating R-loop dynamics could substantially improve the efficacy of stem cell-based therapies. Additionally, we discuss the challenges and future prospects in R-loop research, particularly within the realm of stem cell biology, and underscore the potential therapeutic avenues for targeting R-loop dysregulation. Our findings suggest that a deeper understanding of R-loop biology could lead to novel strategies for enhancing the stability and functionality of stem cells, thereby maximizing their therapeutic outcomes in regenerative medicine and disease treatment.