Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution
Jeffrey B. Cheng,
Andrew J. Sedgewick,
Alex I. Finnegan,
Paymann Harirchian,
Jerry Lee,
Sunjong Kwon,
Marlys S. Fassett,
Justin Golovato,
Matthew Gray,
Ruby Ghadially,
Wilson Liao,
Bethany E. Perez White,
Theodora M. Mauro,
Thaddeus Mully,
Esther A. Kim,
Hani Sbitany,
Isaac M. Neuhaus,
Roy C. Grekin,
Siegrid S. Yu,
Joe W. Gray,
Elizabeth Purdom,
Ralf Paus,
Charles J. Vaske,
Stephen C. Benz,
Jun S. Song,
Raymond J. Cho
Affiliations
Jeffrey B. Cheng
Department of Dermatology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA
Andrew J. Sedgewick
Nantomics, LLC, Culver City, CA, USA
Alex I. Finnegan
Department of Physics, Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
Paymann Harirchian
Department of Dermatology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA
Jerry Lee
Department of Dermatology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA
Sunjong Kwon
Department of Biomedical Engineering, OHSU Center for Spatial Systems Biomedicine, Portland, OR, USA
Marlys S. Fassett
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
Justin Golovato
Nantomics, LLC, Culver City, CA, USA
Matthew Gray
Nantomics, LLC, Culver City, CA, USA
Ruby Ghadially
Department of Dermatology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA
Wilson Liao
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
Bethany E. Perez White
Department of Dermatology and Skin Tissue Engineering Core, Northwestern University, Chicago, IL, USA
Theodora M. Mauro
Department of Dermatology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA
Thaddeus Mully
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
Esther A. Kim
Department of Plastic Surgery, University of California, San Francisco, San Francisco, CA, USA
Hani Sbitany
Department of Plastic Surgery, University of California, San Francisco, San Francisco, CA, USA
Isaac M. Neuhaus
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
Roy C. Grekin
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
Siegrid S. Yu
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
Joe W. Gray
Department of Biomedical Engineering, OHSU Center for Spatial Systems Biomedicine, Portland, OR, USA
Elizabeth Purdom
Department of Statistics, University of California, Berkeley, Berkeley, CA, USA
Ralf Paus
Centre for Dermatology Research, University of Manchester, Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester, UK; Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
Charles J. Vaske
Nantomics, LLC, Culver City, CA, USA
Stephen C. Benz
Nantomics, LLC, Culver City, CA, USA
Jun S. Song
Department of Physics, Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
Raymond J. Cho
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Corresponding author
Summary: Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C+CD301A+ myeloid dendritic cell population in psoriatic epidermis, and IL1βhiCCL3hiCD14+ monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation. : Cheng et al. report single-cell RNA sequencing of normal and inflamed human epidermis, revealing a discrete set of specialized keratinocytes that exhibit a distinct composition at different anatomic sites. Myeloid dendritic cells and macrophages also vary sharply with epidermal anatomic site and inflammation, indicating dynamic programming of antigen-presenting cells. Keywords: epidermis, single-cell RNA-seq, keratinocyte, skin
