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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Epidermis
Skin
Keratinocytes
RNA Sequence Analysis
Macrophages
Myeloid Cells
RNA
Inflammation
Dendritic Cells
Foreskin
Dermatoglyphics
Pathology
Antigen-Presenting Cells
Scalp
Dynamic programming
Skin Diseases
Gene expression
Cell Communication
Homeostasis
Chemical activation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cheng, J. B., Sedgewick, A. J., Finnegan, A. I., Harirchian, P., Lee, J., Kwon, 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

Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution. / Cheng, Jeffrey B.; Sedgewick, Andrew J.; Finnegan, Alex I.; Harirchian, Paymann; Lee, Jerry; Kwon, Sunjong; Fassett, Marlys S.; Golovato, Justin; Gray, Matthew; Ghadially, Ruby; Liao, Wilson; Perez White, Bethany E.; Mauro, Theodora M.; Mully, Thaddeus; Kim, Esther A.; Sbitany, Hani; Neuhaus, Isaac M.; Grekin, Roy C.; Yu, Siegrid S.; Gray, Joe; Purdom, Elizabeth; Paus, Ralf; Vaske, Charles J.; Benz, Stephen C.; Song, Jun S.; Cho, Raymond J.

In: Cell Reports, Vol. 25, No. 4, 23.10.2018, p. 871-883.

Research output: Contribution to journalArticle

Cheng, JB, Sedgewick, AJ, Finnegan, AI, Harirchian, P, Lee, J, Kwon, S, Fassett, MS, Golovato, J, Gray, M, Ghadially, R, Liao, W, Perez White, BE, Mauro, TM, Mully, T, Kim, EA, Sbitany, H, Neuhaus, IM, Grekin, RC, Yu, SS, Gray, J, Purdom, E, Paus, R, Vaske, CJ, Benz, SC, Song, JS & Cho, RJ 2018, 'Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution', Cell Reports, vol. 25, no. 4, pp. 871-883. https://doi.org/10.1016/j.celrep.2018.09.006
Cheng, Jeffrey B. ; Sedgewick, Andrew J. ; Finnegan, Alex I. ; Harirchian, Paymann ; Lee, Jerry ; Kwon, Sunjong ; Fassett, Marlys S. ; Golovato, Justin ; Gray, Matthew ; Ghadially, Ruby ; Liao, Wilson ; Perez White, Bethany E. ; Mauro, Theodora M. ; Mully, Thaddeus ; Kim, Esther A. ; Sbitany, Hani ; Neuhaus, Isaac M. ; Grekin, Roy C. ; Yu, Siegrid S. ; Gray, Joe ; Purdom, Elizabeth ; Paus, Ralf ; Vaske, Charles J. ; Benz, Stephen C. ; Song, Jun S. ; Cho, Raymond J. / Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution. In: Cell Reports. 2018 ; Vol. 25, No. 4. pp. 871-883.
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