The scientific focus of the proposed 3D Multiscale Reference Atlas for Human Skin is to develop the first comprehensive, three-dimensional set of integrated cellular and molecular maps of human skin across age, sex, race and skin location. Skin is the largest human organ, serving as a critical barrier between the external environment and internal tissues, yet no comprehensive map exists for the three-dimensional architecture of this organ at a cellular level, nor is there a comprehensive map of the molecular signatures defining this architecture across the body and across lifespan. Here, we will integrate our recently developed machine learning-guided image analysis system CODA with single-cell and spatial multi-omic analyses to produce high-content reference maps. The integrated Skin Atlas will allow researchers to interrogate the skin in its entire three-dimensional architecture, and/or focus on individual structures such as the vasculature or hair follicles, or individual cells. We will overlay genotypic and phenotypic states to enable, for example, examination of the overlap between senescent cells and stem cells, or the correlation between extracellular matrix (ECM) content and the diversity of dermal fibroblasts. Because we will include diverse and often underrepresented populations, our Multiscale Atlas will also provide a broader view of skin biology, filling in critical missing information. Finally, by looking across lifespan, the Atlas will provide a view of architectural, cellular, and molecular alterations in skin with age, establishing the natural history of normal biology for this critical organ. In addition to its native value for understanding skin itself, we anticipate that our Skin Atlas will be a powerful hypothesis generating tool for biologists studying the many questions for which skin is an ideal model system – homeostatic renewal, repair, senescence, aging, and pathogen response.

Narrative We propose to create a center at Johns Hopkins University that will produce the first large-volume integrated three-dimensional maps of the human skin as a function of age, race, and sex.