Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
International Research Center of Wound Repair and Regeneration (iWRR), National Cheng Kung University, Tainan, Taiwan.
Nat Commun. 2021 May 10;12(1):2595. doi: 10.1038/s41467-021-22822-9.
Tissue regeneration is a process that recapitulates and restores organ structure and function. Although previous studies have demonstrated wound-induced hair neogenesis (WIHN) in laboratory mice (Mus), the regeneration is limited to the center of the wound unlike those observed in African spiny (Acomys) mice. Tissue mechanics have been implicated as an integral part of tissue morphogenesis. Here, we use the WIHN model to investigate the mechanical and molecular responses of laboratory and African spiny mice, and report these models demonstrate opposing trends in spatiotemporal morphogenetic field formation with association to wound stiffness landscapes. Transcriptome analysis and K14-Cre-Twist1 transgenic mice show the Twist1 pathway acts as a mediator for both epidermal-dermal interactions and a competence factor for periodic patterning, differing from those used in development. We propose a Turing model based on tissue stiffness that supports a two-scale tissue mechanics process: (1) establishing a morphogenetic field within the wound bed (mm scale) and (2) symmetry breaking of the epidermis and forming periodically arranged hair primordia within the morphogenetic field (μm scale). Thus, we delineate distinct chemo-mechanical events in building a Turing morphogenesis-competent field during WIHN of laboratory and African spiny mice and identify its evo-devo advantages with perspectives for regenerative medicine.
组织再生是一个重现和恢复器官结构和功能的过程。尽管先前的研究已经在实验小鼠(Mus)中证明了创伤诱导的毛发新生(WIHN),但与在非洲刺鼠(Acomys)中观察到的情况不同,这种再生仅限于伤口的中心。组织力学已被认为是组织形态发生的一个组成部分。在这里,我们使用 WIHN 模型来研究实验和非洲刺鼠的机械和分子反应,并报告这些模型表现出与伤口硬度景观相关的时空形态发生场形成的相反趋势。转录组分析和 K14-Cre-Twist1 转基因小鼠表明,Twist1 途径作为表皮-真皮相互作用的介质和周期性模式形成的能力因素发挥作用,这与发育过程中使用的途径不同。我们提出了一个基于组织刚度的图灵模型,该模型支持一个两尺度组织力学过程:(1)在伤口床上建立形态发生场(毫米尺度),(2)表皮的对称破缺和在形态发生场中形成周期性排列的毛发原基(微米尺度)。因此,我们在实验室和非洲刺鼠的 WIHN 过程中描绘了构建图灵形态发生能力场的不同化学机械事件,并确定了其在再生医学方面的进化优势。
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