Dataset Information

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 here the quantitative distribution of structural proteins, known and novel proteins specific to cellular subsets and those with specialized immunological funtions such as cytokines and chemokines. We anticipate this proteomic atlas of human skin will become an essential community resource for basic and translational research (www.skin.science).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Melanocyte, Dendritic Cell, Epithelial Cell, Keratinocyte, Skin, Fibroblast, Macrophage

SUBMITTER: Fabian Coscia

LAB HEAD: Matthias Mann

PROVIDER: PXD019909 | Pride | 2020-11-18

REPOSITORIES: Pride

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Publications

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

Dyring-Andersen Beatrice B Løvendorf Marianne Bengtson MB Coscia Fabian F Santos Alberto A Møller Line Bruun Pilgaard LBP Colaço Ana R AR Niu Lili L Bzorek Michael M Doll Sophia S Andersen Jørgen Lock JL Clark Rachael A RA Skov Lone L Teunissen Marcel B M MBM Mann Matthias M

Nature communications 20201105 1

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 10,7 ...[more]

PMID: 33154365

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Project description:Papillomaviruses (PVs) are able to induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), naturally infects NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice. C57BL/6J wild-type mice were not susceptible to MmuPV1 infection; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu but not NU/J-Foxn1nu mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, that lack B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Although lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail and condylomas of the vaginal lining could be induced by experimental infections. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Surprisingly, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were dramatically dysregulated. To determine if there were transcriptome differences between papillomas on the tail skin compared to invasive trichoblastomas on the dorsal skin, tumors from the tail and dorsal skin from 3 B6.Cg-Foxn1nu/Foxn1nu mice and unaffected skin from the tail or contra-lateral (dorsal skin) were compared using the Affymetrix GeneChip Mouse Genome 1.0 ST Array. Concurrently, a matched study was done at the University of Louisville comparing facial (muzzle) papillomas and dorsal skin trichoblastomas to respective unaffected contralateral skin.

Dataset Information

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

Publications

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

Similar Datasets

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