In vivo gene signature of TLR3KO mice stimulated by ethanol (EtOH) or all trans retinoic acid (atRA) treatment

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate entirely new hair follicles de novo following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor TLR3 to induce intrinsic retinoic acid (RA) synthesis in a gradient that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a novel stimulus for retinoic acid synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity. The goal of this experiment is to investigate the profile of gene expression rescued by atRA in TLR3KO mice. Two TLR3KO mice at telogen stage were wounded on back skin with 1.2 cm2 size. Next day (wound day 1-WD1), 30 ul of EtOH or 0.1 ug/30 ul of atRA was locally treated onto wounded skin of one TLR3KO mouse.