Symmetry breaking of tissue mechanics in wound induced hair follicle regeneration [scRNA-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 (um 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. Single-cell mRNA sequencing for back skin from naive mice using Drop-Seq组织再生是一个重现发育与演化过程中分子与力学特征的生物学过程。本研究采用创伤诱导性毛发新生（wound-induced hair neogenesis, WIHN）模型，探究实验室小鼠（Mus，小家鼠属）与非洲刺小鼠（Acomys，刺毛鼠属）的力学与分子应答特征。在创伤愈合过程中，两类小鼠的创伤诱导性毛发新生时空形态发生场呈现截然相反的变化趋势；全创伤床的创伤刚度梯度可预测毛发形成的空间模式。本研究通过批量RNA测序（bulk RNA-seq）与单细胞RNA测序（single-cell RNA-seq）分析，结合K14-Cre-Twist1转基因小鼠模型，明确了Twist1通路作为表皮-真皮相互作用介导因子与周期性毛发原基形成核心调控通路的关键作用。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，解释两类过程：一是从创伤床（毫米级）形成形态发生场，二是从形态发生场生成周期性排布的毛发原基（微米级）。解析实验室小鼠与非洲刺小鼠再生性创伤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（evolutionary developmental biology, evo-devo）层面的优势，为再生医学领域提供全新研究视角。本研究采用Drop-Seq技术对未经过实验处理的小鼠背部皮肤开展单细胞mRNA测序。