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. GrayElizabeth Purdom, Ralf Paus, Charles J. Vaske, Stephen C. Benz, Jun S. Song, Raymond J. Cho

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)871-883
Number of pages13
JournalCell Reports
Volume25
Issue number4
DOIs
StatePublished - Oct 23 2018

Keywords

  • epidermis
  • keratinocyte
  • single-cell RNA-seq
  • skin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution'. Together they form a unique fingerprint.

  • Cite this

    Cheng, J. B., Sedgewick, A. J., Finnegan, A. I., Harirchian, P., Lee, J., Kwon, S., Fassett, M. S., Golovato, J., Gray, M., Ghadially, R., Liao, W., Perez White, B. E., Mauro, T. M., Mully, T., Kim, E. A., Sbitany, H., Neuhaus, I. M., Grekin, R. C., Yu, S. S., ... Cho, R. J. (2018). Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution. Cell Reports, 25(4), 871-883. https://doi.org/10.1016/j.celrep.2018.09.006