Dynamic regulation of tissue fluidity controls skin repair during wound healing [bulk RNA-seq]

During wounding healing, different pools of stem cells (SCs) During homeostasis, different compartments of the epidermis are sustained by distinct pools of stem cells (SC) whereas, upon wounding, these different 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 while leaving the basic organization of the skin intact, 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 remodelling during repair, as predicted by a minimal mathematical modelling of the spatiotemporal dynamics and fate behaviour of the basal cells population. The basal cell layer progressively returns to a solid-like state with re-epithelialization and the restoration of barrier function. 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.