Defining stem cell dynamics and migration during wound healing in mouse skin epidermis

Abstract

Wound healing is essential to repair the skin after injury. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. However, how SCs balance proliferation, differentiation and migration to repair a wound remains poorly understood. Here, we show the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, we identify the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound. Functional experiments show that SC proliferation, migration and differentiation can be uncoupled during wound healing. Lineage tracing and quantitative clonal analysis reveal that, following wounding, progenitors divide more rapidly, but conserve their homoeostatic mode of division, leading to their rapid depletion, whereas SCs become active, giving rise to new progenitors that expand and repair the wound. These results have important implications for tissue regeneration, acute and chronic wound disorders.

Skin and Its Regenerative Powers: An Alliance between Stem Cells and Their Niche

“…Immunofluorescence analyses of back skin and intravital videomicroscopy of ear skin shows that the process begins at ~12 hr post wounding with migration rates being highest (~1.6 µm/day) at the wound edge by day 3 (Aragona et al, 2017; Keyes et al, 2016; Park et al, 2017). By contrast, in a fashion similar to that seen in closure of the embryonic epidermis over the eyelid (Heller et al, 2014), the proliferative response occurs in the region behind and only partially overlapping with the migrating epidermal front (Park et al, 2017).…”

Reconstruction of Cell Focal Adhesions using Physical Constraints and Compressive Regularization

“…After further regrouping terms, we find a linear system of equations for u s (x, y) across all grid points. For example, (6) where summation notation for each index tuple (j, k) has been implicitly assumed, and the tensors Γ nmjk xx , Γ nmjk xy , and the analogous formulae for u y (x n , y m ) are given in Appendix B of the Supplementary Material.…”

“…6 highly ill-conditioned. 6 To resolve these issues, we introduce a number of physically consistent constraints and regularization terms relevant to this system.…”

“…The adhesion of cells and tissues to their environment has profound consequences on processes such as cell polarization [1], division, differentiation [2], tissue morphology during development [3], wound healing [4][5][6], and cancer metastasis [7]. Hence, quantifying how cells attach to impart force on the surrounding material is an important technical challenge in cell biology.…”

“…to migration in wound healing assays [4][5][6]. Dynamically varying force-generating structures are often small and difficult to image.…”