%0 Journal Article
%A He, Helen
%A Suryawanshi, Hemant
%A Morozov, Pavel
%A Gay-Mimbrera, Jesús
%A Del Duca, Ester
%A Kim, Hyun Je
%A Kameyama, Naoya
%A Estrada, Yeriel
%A Der, Evan
%A Krueger, James G
%A Ruano, Juan
%A Tuschl, Thomas
%A Guttman-Yassky, Emma
%T Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis.
%D 2020
%U http://hdl.handle.net/10668/15077
%X Atopic dermatitis (AD) is a prevalent inflammatory skin disease with a complex pathogenesis involving immune cell and epidermal abnormalities. Despite whole tissue biopsy studies that have advanced the mechanistic understanding of AD, single cell-based molecular alterations are largely unknown. Our aims were to construct a detailed, high-resolution atlas of cell populations and assess variability in cell composition and cell-specific gene expression in the skin of patients with AD versus in controls. We performed single-cell RNA sequencing on skin biopsy specimens from 5 patients with AD (4 lesional samples and 5 nonlesional samples) and 7 healthy control subjects, using 10× Genomics. We created transcriptomic profiles for 39,042 AD (lesional and nonlesional) and healthy skin cells. Fibroblasts demonstrated a novel COL6A5+COL18A1+ subpopulation that was unique to lesional AD and expressed CCL2 and CCL19 cytokines. A corresponding LAMP3+ dendritic cell (DC) population that expressed the CCL19 receptor CCR7 was also unique to AD lesions, illustrating a potential role for fibroblast signaling to immune cells. The lesional AD samples were characterized by expansion of inflammatory DCs (CD1A+FCER1A+) and tissue-resident memory T cells (CD69+CD103+). The frequencies of type 2 (IL13+)/type 22 (IL22+) T cells were higher than those of type 1 (IFNG+) in lesional AD, whereas this ratio was slightly diminished in nonlesional AD and further diminished in controls. AD lesions were characterized by expanded type 2/type 22 T cells and inflammatory DCs, and by a unique inflammatory fibroblast that may interact with immune cells to regulate lymphoid cell organization and type 2 inflammation.
%K Atopic dermatitis
%K T cells
%K cytokines
%K dendritic cells
%K fibroblasts
%K single-cell RNA sequencing
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