Symmetry breaking of tissue mechanics in wound induced hair follicle regeneration [bulk RNA-seq]

Tissue regeneration is a process that recapitulates the molecular and mechanical aspects of development and evolution. We use the wound-induced hair neogenesis (WIHN) model to investigate the mechanical and molecular responses of the laboratory (Mus) and African spiny (Acomys) mice. Laboratory and spiny mice showed an opposite trend of spatiotemporal morphogenetic field for WIHN during wound healing, and wound stiffness gradient across the whole wound bed predicated pattern of hair formation. Using bulk and single-cell RNA-seq analysis and K14-Cre-Twist1 transgenic mice, we identified the central role of the Twist1 pathway as the mediator of epidermal-dermal interaction and the emergence of periodic hair primordia. Lastly, we generated a Turing model with an underlying measure of stiffness to support a two-scale tissue mechanic model to explain the setup of a morphogenetic field from a wound bed (mm scale) or periodically arranged hair primordia from a morphogenetic field (μm scale). Delineating the common and distinct chemo-mechanical events during regenerative wound healing between laboratory and African spiny mice reveal its evo-devo advantages, which provide new perspectives for regenerative medicine.

组织再生（Tissue regeneration）是一类重现发育与演化进程中分子与力学特征的生理过程。本研究采用创伤诱导性毛发新生（wound-induced hair neogenesis, WIHN）模型，探究实验小鼠（Mus）与非洲刺毛鼠（Acomys）的力学与分子响应规律。实验小鼠与非洲刺毛鼠在创面愈合过程中，其介导WIHN过程的时空形态发生场呈现截然相反的变化趋势；全创面床的创面刚度梯度可预测毛发形成模式。本研究通过批量及单细胞RNA测序（bulk and single-cell RNA-seq）分析结合K14-Cre-Twist1转基因小鼠模型，明确了Twist1信号通路作为表皮-真皮相互作用介导因子与周期性毛囊原基形成核心调控元件的关键作用。最后，本研究构建了纳入刚度量化指标的图灵模型（Turing model），以支撑双尺度组织力学模型，该模型可解释从创面床（毫米级）构建形态发生场，以及从形态发生场形成周期性排布毛囊原基（微米级）的分子机制。厘清实验小鼠与非洲刺毛鼠再生性创面愈合过程中共通与独特的化学-力学事件，可揭示其进化发育生物学（evo-devo）层面的研究优势，为再生医学提供全新的研究视角。