Dynamic regulation of tissue fluidity controls skin repair during wound healing.

During wound healing, different pools of stem cells (SCs) contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging. Analysis of basal cell rearrangements shows dynamic transitions from a solid-like homeostatic state to a fluid-like state allowing tissue remodeling during repair, as predicted by a minimal mathematical modeling of the spatiotemporal dynamics and fate behavior of basal cells. The basal cell layer progressively returns to a solid-like state with re-epithelialization. Bulk, single-cell RNA, and epigenetic profiling of SCs, together with functional experiments, uncover a common regenerative state regulated by the EGFR/AP1 axis activated during tissue fluidization that is essential for skin SC activation and tissue repair. [Display omitted] • Clonal analysis after cell ablation uncovers dynamic of skin SCs during tissue repair • Mathematical modeling supports a density-dependent promotion of symmetric SC division • Wound healing involves dynamic changes in tissue fluidity • EGFR/AP1 axis controls a regenerative state that regulates tissue fluidity and repair During skin wound repair, the basal cell layer transitions from a solid-like homeostatic state to a fluid-like state that allows tissue remodeling during repair and then progressively returns to a solid-like state with re-epithelialization. [ABSTRACT FROM AUTHOR]