School of Molecular Biosciences, Washington State University, Pullman, United States.
Center for Reproductive Biology, Washington State University, Pullman, United States.
Elife. 2020 Sep 29;9:e60066. doi: 10.7554/eLife.60066.
Scars are a serious health concern for burn victims and individuals with skin conditions associated with wound healing. Here, we identify regenerative factors in neonatal murine skin that transforms adult skin to regenerate instead of only repairing wounds with a scar, without perturbing development and homeostasis. Using scRNA-seq to probe unsorted cells from regenerating, scarring, homeostatic, and developing skin, we identified neonatal papillary fibroblasts that form a transient regenerative cell type that promotes healthy skin regeneration in young skin. These fibroblasts are defined by the expression of a canonical Wnt transcription factor Lef1 and using gain- and loss of function genetic mouse models, we demonstrate that Lef1 expression in fibroblasts primes the adult skin macroenvironment to enhance skin repair, including regeneration of hair follicles with arrector pili muscles in healed wounds. Finally, we share our genomic data in an interactive, searchable companion website (https://skinregeneration.org/). Together, these data and resources provide a platform to leverage the regenerative abilities of neonatal skin to develop clinically tractable solutions that promote the regeneration of adult tissue.
疤痕是烧伤患者和与伤口愈合相关的皮肤状况患者的严重健康问题。在这里，我们鉴定了新生鼠皮肤中的再生因子，这些因子可使成人皮肤再生，而不是仅形成疤痕来修复伤口，同时不破坏发育和体内平衡。我们使用 scRNA-seq 对再生、疤痕、稳态和发育中的皮肤进行未分选细胞探测，鉴定出了在新生皮肤中形成短暂再生细胞类型的乳头状成纤维细胞，该细胞类型可促进年轻皮肤的健康再生。这些成纤维细胞的特征是表达经典的 Wnt 转录因子 Lef1，通过获得和丧失功能的遗传小鼠模型，我们证明成纤维细胞中 Lef1 的表达使成年皮肤宏环境为增强皮肤修复做好准备，包括在愈合伤口中再生带有竖毛肌的毛囊。最后，我们在一个交互式、可搜索的配套网站（https://skinregeneration.org/）上共享我们的基因组数据。总之，这些数据和资源为利用新生儿皮肤的再生能力来开发临床可行的解决方案以促进成人组织再生提供了一个平台。
