Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3
Date
2019-12-01Journal
Nature CommunicationsPublisher
Nature Publishing GroupType
Article
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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. © 2019, The Author(s).Sponsors
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases under R01AR064297 and AR068280, Armed Forces Institute of Regenerative Medicine, Extremities Regeneration AFIRM2-ER11, CDMRMP W81XWH-16-C-0167, Maryland Stem Cell Research Grant (2017-MSCRFF-3905), Eunice Kennedy Shriver National Institute of Child Health and Human Development under R01HD077260 and by the University of Maryland School of Pharmacy Mass Spectrometry Center (SOP1841-IQB2014).Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85067973042&origin=inward; http://hdl.handle.net/10713/9864ae974a485f413a2113503eed53cd6c53
10.1038/s41467-019-10811-y