Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis.
Helen He, Hemant Suryawanshi, Pavel Morozov, Jesús Gay-Mimbrera, Ester Del Duca, Hyun Je Kim, Naoya Kameyama, Yeriel Estrada, Evan Der, James G Krueger, Juan Ruano, Thomas Tuschl, Emma Guttman-Yassky
Author Information
Helen He: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Hemant Suryawanshi: Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY. Electronic address: hsuryawans@mail.rockefeller.edu.
Pavel Morozov: Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY.
Jesús Gay-Mimbrera: Department of Dermatology, Reina Sofía University Hospital, Córdoba, Spain.
Ester Del Duca: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Hyun Je Kim: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Naoya Kameyama: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Yeriel Estrada: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Evan Der: Division of Rheumatology and Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY.
James G Krueger: Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY.
Juan Ruano: Department of Dermatology, Reina Sofía University Hospital, Córdoba, Spain.
Thomas Tuschl: Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY. Electronic address: ttuschl@rockefeller.edu.
Emma Guttman-Yassky: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: emma.guttman@mountsinai.org.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: We created transcriptomic profiles for 39,042 AD (lesional and nonlesional) and healthy skin cells. Fibroblasts demonstrated a novel COL6A5COL18A1 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 (CD1AFCER1A) and tissue-resident memory T cells (CD69CD103). 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. CONCLUSION: 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.
