Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
Nat Commun. 2019 Jun 26;10(1):2811. doi: 10.1038/s41467-019-10811-y.
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.
发育程序如何在再生中重新激活是生物学中的一个基本问题。我们通过研究创伤诱导的毛囊新生（WIHN）来解决这个问题，这是一种成年器官发生模型，其中干细胞在深度创伤后会从头再生毛囊。确切的机制尚不确定。在这里，我们表明自我非编码 dsRNA 激活抗病毒受体 Toll 样受体 3（TLR3），以诱导内在视黄酸（RA）合成，这种模式可预测小鼠创伤后新毛囊的形成。此外，在人类中，再生激光会诱导 dsRNA 和 RA 的基因表达特征，内在 RA 合成可测量增加。这些结果表明非编码 dsRNA 对 RA 合成具有强大的刺激作用，这与其在发育和免疫中的广泛功能有关。
