210 Three-dimensional models of human skin at single-cell resolution in health and disease

The human skin is a complex three-dimensional tissue comprised of an outer layer, the epidermis includes keratinocytes, melanocytes and Langerhans cells, with an underlying connective tissue layer, the dermis which contains numerous cell types such as fibroblasts, endothelial cells and immune populations. As for many human tissues, the structure and function is determined by complex interactions between these diverse cell types. In recent years, advances in single cell genomics and computational methods have facilitated a revolution in the ability to analyse transcriptional profiles at the single cell level. However dissecting to what extent observed transcriptional identify is specified intrinsically rather than dictated by the local cellular and extracellular matrix environment remains a significant challenge for the field. As part of the Human Cell Atlas project – an international collaborative effort to map all cell types within the human body – single cell RNA sequencing has been performed on in excess of a hundred thousand cells from the epidermis and dermis from human skin derived from healthy individuals using the chromium 10X platform. This has enabled the identification of novel cellular subtypes. In order to understand the factors governing cellular identity in healthy and diseased skin, we are integrating computational and ex vivo strategies with in vivo dynamic optical computed tomography skin imaging to probe the relative importance of intrinsic and extrinsic factors in in three-dimensional human tissues. In future work, we will apply these methods to skin diseases including psoriasis, eczema and lichen planus with the goal of understanding the changes in cellular identity that accompany disease pathogenesis.