Endogenous dsRNA Co-IP in SHG cells

Double-stranded RNA (dsRNA) is an established trigger of innate immunity, activating intrinsic and extrinsic cellular response mechanisms. While this response is typically associated with viral infection, it has also been shown that accumulation of self-derived dsRNAs known as endoge-nous dsRNA, also have the capacity to activate similar innate pathways. However, the extent to which endogenous dsRNA is dynamically regulated during normal cellular non-immune homeo-stasis, as opposed to pathological states, remains poorly understood. This raises important ques-tions about the physiological roles of dsRNA and the mechanisms that restrain its immunostimu-latory potential. Here, we aim to characterize the presence of endogenous dsRNA within the skin at steady state and understand its accumulation during differentiation, wound healing and within hair follicle stem cell niches. We find that dsRNA is predominantly localized to basal progenitor epidermal keratinocytes under homeostatic conditions and is upregulated in wound healing areas that later harbor neogenic hair follicle morphogenesis. Notably, we also observed upregulation of dsRNA during a transient state of hair follicle stem cell activation, suggesting a role in maintain-ing progenitor multipotency and directing early differentiation. Given the essential role of dsRNA and its capacity to induce regeneration, uncovering the mechanisms that govern its accumulation will reveal the regulatory machinery that influences cell fate and holds therapeutic potential.