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 combine advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantify 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 previously undescribed 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 (https://skin.science/).

Human Amniotic Fluid Stem Cell-Derived Exosomes as a Novel Cell-Free Therapy for Cutaneous Regeneration

“…The skin provides a natural and significant protective barrier for the human body. However, severe disabilities or even death may occur if its integrity is damaged ( Coughlin and Taïeb, 2014 ; Dyring-Andersen et al, 2020 ). The ultimate goal of wound therapy is to rapidly close and shape the lesion and functionally restore the skin ( Reinke and Sorg, 2012 ; Sorg et al, 2017 ).…”

Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis

“…2 A). Genes regulated at both time-points included inflammatory cytokines such as IL-6, IL-36RN, IL-36G (expressed predominantly in the outer epidermis) [ 76 ] and NOLC1 which are associated with both acute phase response and pro-apoptotic signalling ( Supplementary Table 1 ; Supplementary Table 2 ). Differential upregulation of acute phase response signalling in response to UVB in psoriasis is particularly interesting as lesional skin does not develop visible erythema even in response to doses many times in excess of the patient's MED [ 15 ], and, importantly, doses of 311 nm and 290 nm UVB were matched for their erythemogenic potential (in uninvolved skin).…”

Current State of SLC and ABC Transporters in the Skin and Their Relation to Sweat Metabolites and Skin Diseases

“…With the development of mass spectrometry (MS) analysis, we can now use MS-based proteomics approaches as a tool for quantification and identification of proteins in humans [39,40]. The advances in this technology have also allowed higher sensitivity when characterizing and analyzing large proteomes [41,42]. Knowledge about skin composition, especially the role of many transporters found in the skin, is limited.…”

“…Knowledge about skin composition, especially the role of many transporters found in the skin, is limited. Recent studies have used proteomic investigation to try to capture the complexity of the skin [41]. The layered composition comprising of the inner and outer epidermis has been studied using in-depth MS-based proteomics utilizing both data-dependent acquisition and data-independent acquisition approaches.…”

“…The layered composition comprising of the inner and outer epidermis has been studied using in-depth MS-based proteomics utilizing both data-dependent acquisition and data-independent acquisition approaches. Using proteomics to investigate skin cell type diversity, including keratinocytes, fibroblasts, melanocytes, endothelial, and immune cells, revealed quantification of a total of 10,701 proteins and these findings have provided essential information for the unique systems and functions of each cell type within the skin complex [41].…”