Abstract
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 de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern 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 potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.
Highlights
How developmental programs reactivate in regeneration is a fundamental question in biology
We noted that many of these gene transcripts were involved in keratinocyte differentiation; KERATIN19 (KRT19) is a marker of basal keratinocyte stem cells residing in the hair follicle bulge compartment
We found a similar pattern where genes like tumor protein p63 (TP63/p63) were induced; it is among the earliest transcription factors to define an epidermal fate during development
Summary
How developmental programs reactivate in regeneration is a fundamental question in biology. We use the model of wound-induced hair neogenesis (WIHN) to identify mechanisms of reactivating developmental pathways in adult regeneration. We reported that damaged skin activates Toll Like Receptor 3 (TLR3) signaling to induce hair follicle regeneration[9] Together, these findings suggest that in addition to other pathways, TLR3 signaling as a damage sensor might connect stem cell activity to regeneration. Among other uses, RA is commonly used clinically for facial esthetic rejuvenation[14], as are a variety of other skin damaging treatments such as dermabrasion or laser resurfacing These data indicate that RA biologically acts as an essential morphogen in development and regeneration, but, interestingly, its clinical use overlaps that with damage-inducing therapies. We show evidence in both humans and mice that a dsRNA-RA axis is a conserved pathway for promoting rejuvenation or regeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
