Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin

Abstract

Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combined advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantified 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and novel proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research (www.skin.science).

Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis

“…Methodologies such as those used in this and many other studies now allow for similar investigations of other human skin diseases, hopefully resulting in an increasingly refined Human Cell Atlas and Human Skinatlas. 65,66 Most importantly, these new technologies have taught us that the mechanisms operative in skin physiology and pathology are flexible processes and highly diverse between different persons and that a successful interference with these will require individualized approaches.…”

Anatomical structures, cell types and biomarkers of the Human Reference Atlas

“…[78][79][80][81][82][83][84][85][86] and Sun, X. & Morrisey, E., manuscript in preparation), lymph nodes [87][88][89][90][91][92][93][94][95][96][97] , skin [98][99][100][101][102][103][104][105][106][107][108][109][110] , spleen 89,[111][112][113][114][115][116][117][118][119][120][121][122] , thymus [123][124][125][126][127]…”

Species-specific cutaneous protein signatures upon incision injury and correlation with distinct pain-related phenotypes in humans

“…However, the transcriptome and proteome correspondence is known to be limited, with consequential challenges to predict functional alterations on the mRNA level (33)(34)(35). Recent excellent work by Dyring-Andersen and colleagues has reported detailed molecular profiles of distinct human skin cell types on the protein level in healthy volunteers (65). Our work considerably extends these efforts by providing (i) inter-species proteome profiles, (ii) altered inter-species protein signatures upon incision-injury, and (iii) their correlation with pain-associated phenotypes in human volunteers.…”