P18 Facial dermis has distinct extracellular matrix influencing biomechanical tissue properties and cell behaviours
Claire Piper, Claudia Clara, Willow Hight-Warburton, Karen Liu, Anthony Graham, Tanya ShawAbstract
Introduction and aims
Skin of the face is indisputably different from other regions of the body; for example, it is highly innervated and vascularized, and anecdotally superior at repair/regeneration. We propose that positionally distinct dermal features reflect the developmental origins of the tissue, with facial dermis uniquely derived from neural crest, and not mesoderm as in the rest of the body. We previously reported bulk tissue RNA sequencing indicating that cheek dermis differences include a distinct extracellular matrix (ECM), but the functional implications are not known.
Methods
Bioinformatic analyses of diverse transcriptomic data representing face vs. body dermis/fibroblasts provided insight about functions and regulatory mechanisms. The effect of the anatomically variable ECM on tissue biomechanics was tested by enzymatic digestion and nanoindentation. Primary cell/tissue culture and in vivo experiments link the variable ECM with distinct cell behaviours.
Results
RNA sequencing analysis of mouse and human dermis and dermal fibroblasts from face and body sites discovered remarkably consistent site-specific signatures. Functional classification of the differentially expressed genes revealed the ECM to be significantly altered. The functional consequences were demonstrated by susceptibility to collagenase digestion: cheek dermis was rapidly degraded relative to back/abdomen implying fragility/softness. Nanoindentation validated that cheek dermis is less stiff. Culture of freshly isolated primary mouse fibroblasts (cheek vs. back) on soft (2kPa) vs. stiff (32kPa) substrates uncovered divergent mechanoresponses, including many transcriptional differences with potential to influence wound/scar outcomes. Implications of the ECM differences on cell migration were detected during explant cultures; fibroblast emigration was significantly more consistent and faster in cheek vs. back dermis. Similarly, histological analysis of tissue repopulation during wound healing showed faster migration of cheek fibroblasts out of wound-edge dermis into the wound bed.
Conclusions
This work builds upon recognized anatomical and developmental variations in skin and highlights the ECM as a key influential variable.