Abstract:
Transposable elements (TEs), once considered mere genomic relics of ancient viruses, are now recognized as dynamic regulators of gene expression, chromatin organization and innate immunity. This dissertation explores their context-dependent role in tissue regeneration, focusing on two contrasting settings: acute bone fracture healing and chronic muscle degeneration in Duchenne muscular dystrophy. In the bone model, TE reactivation was transiently induced during the early inflammatory phase, correlating with enhanced bone mineralization. In vitro, delivery of full-length LINE-1 (L1) RNA elicited a short-lived inflammatory response that promoted osteoblast mineral matrix deposition, suggesting that controlled TE activation supports physiological inflammation required for repair. In contrast, dystrophic muscle displayed persistent L1 upregulation in myogenic progenitors, driving chronic inflammation and senescence through aberrant activation of innate immunity. Targeted L1 silencing mitigated these effects, increasing myogenic potential. Overall, these findings reveal that TE activity can act as both a facilitator and disruptor of tissue homeostasis, depending on its duration and context, placing transposons at the intersection of inflammation and regeneration.

Bio:
Gabriele Morelli is a PhD candidate in Prof. Valerio Orlando’s lab, where his research investigates the role of transposable elements in tissue regeneration. He combines in vitro experimental work with animal research to study how transposable element regulation influences inflammation and repair following tissue injury.