573 Hair follicles employ a 2-dimensional healing strategy to repair 3-dimensional injuries

Abstract

Epithelial organs vary from 2-dimensional sheets to 3-dimensional folded architectures. While wounds in 2-dimensional sheets are healed through collective movement along the basement membrane (BM), how injuries in 3-dimensional architecture are repaired remains elusive. Using post-radiation anagen hair follicle repair (AHFR), we studied this process through multiphoton intravital imaging. Before radiation, the growth of hair follicles (HFs) is primarily supported by proliferative germinative/matrix cells surrounding dermal papilla at the base. Upon radiation, these cells became apoptotic. In response to cell loss, basal outer root sheath cells/lower proximal cup cells on the cylindrical wall that were normally immotile became motile for internal structure regeneration. Interestingly, they did not take the shortest route by penetrating through the internal layers but moved along the outer cylindrical surface plane toward the injured zone. Additionally, unlike the healing on planar sheets, these cells did not move collectively, but rather independently and stochastically along the preserved BM. Through topological transformation, we found that the observed 3-dimensional regeneration process could still be mapped to 2-dimensional motion on a virtual plane, resembling the conventional 2-dimensional healing process. Mathematical modeling showed that this strategy allowed for long-range cell communication to replenish stochastic cell loss while maintaining the 3-dimensional organ architecture. Thus, this simplified healing strategy of AHFR enables timely regeneration in 3-dimensional HFs to resume the same anagen and bypasses the need for hair cycle resetting.