Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Life Sciences and Systems Biology, Molecular Biotechnology Centre, University of Turin, Turin, Italy.
EMBO Rep. 2021 Jul 5;22(7):e50882. doi: 10.15252/embr.202050882. Epub 2021 Jun 4.
Injury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that HF development can be sacrificed for the sake of epidermal wound regeneration. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.
成人组织中的损伤通常会重新激活发育程序以促进再生，但尚不清楚这一模式是否适用于生长中的组织。在这里，我们通过水疱的方法表明，表皮伤口的愈合是以皮肤发育为代价的。再生的表皮抑制了组织形态发生基因的表达，同时伴随着毛囊（HF）生长的延迟。谱系追踪实验、细胞增殖动力学和数学建模表明，经历形态转化的 HF 连接区干细胞的后代修复水疱，而不促进 HF 发育。相比之下，HF 间充质干细胞后代对水疱愈合的贡献较小。这些发现表明，HF 发育可以为表皮伤口再生而牺牲。我们的研究阐明了皮肤水疱病中伤口愈合的关键细胞机制。
