RNA signaling in cellular plasticity during homeostasis and regeneration

Cells and tissues constantly read and broadcast information through RNA. This mini-review explores how endogenous and damage-released RNAs act as instructive signals that rewire cell identity during steady-state homeostasis and injury repair. We will cover how repetitive-element-derived RNAs and regulatory long-noncoding RNAs (lncRNAs) tune stem and progenitor plasticity in hematopoietic, pluripotent, and muscle systems by coupling stress sensing to cell-fate decisions. We will also outline extracellular dsRNA/TLR3 signaling and injury-induced lncRNAs in epithelial, neural, cardiac, and vascular regeneration, and show how extracellular RNA shapes inflammatory and stromal responses. Together, these concepts present RNA as an active rheostat of cellular plasticity across development, tissue maintenance, and regeneration.