Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes
Alexander A. Merleev, … , Johann E. Gudjonsson, Emanual Maverakis
Alexander A. Merleev, … , Johann E. Gudjonsson, Emanual Maverakis
Published July 28, 2022
Citation Information: JCI Insight. 2022;7(16):e159762. https://doi.org/10.1172/jci.insight.159762.
View: Text | PDF
Resource and Technical Advance Dermatology

Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes

  • Text
  • PDF
Abstract

The epidermis is the outermost layer of skin. Here, we used targeted lipid profiling to characterize the biogeographic alterations of human epidermal lipids across 12 anatomically distinct body sites, and we used single-cell RNA-Seq to compare keratinocyte gene expression at acral and nonacral sites. We demonstrate that acral skin has low expression of EOS acyl-ceramides and the genes involved in their synthesis, as well as low expression of genes involved in filaggrin and keratin citrullination (PADI1 and PADI3) and corneodesmosome degradation, changes that are consistent with increased corneocyte retention. Several overarching principles governing epidermal lipid expression were also noted. For example, there was a strong negative correlation between the expression of 18-carbon and 22-carbon sphingoid base ceramides. Disease-specific alterations in epidermal lipid gene expression and their corresponding alterations to the epidermal lipidome were characterized. Lipid biomarkers with diagnostic utility for inflammatory and precancerous conditions were identified, and a 2-analyte diagnostic model of psoriasis was constructed using a step-forward algorithm. Finally, gene coexpression analysis revealed a strong connection between lipid and immune gene expression. This work highlights (a) mechanisms by which the epidermis is uniquely adapted for the specific environmental insults encountered at different body surfaces and (b) how inflammation-associated alterations in gene expression affect the epidermal lipidome.

Authors

Alexander A. Merleev, Stephanie T. Le, Claire Alexanian, Atrin Toussi, Yixuan Xie, Alina I. Marusina, Steven M. Watkins, Forum Patel, Allison C. Billi, Julie Wiedemann, Yoshihiro Izumiya, Ashish Kumar, Ranjitha Uppala, J. Michelle Kahlenberg, Fu-Tong Liu, Iannis E. Adamopoulos, Elizabeth A. Wang, Chelsea Ma, Michelle Y. Cheng, Halani Xiong, Amanda Kirane, Guillaume Luxardi, Bogi Andersen, Lam C. Tsoi, Carlito B. Lebrilla, Johann E. Gudjonsson, Emanual Maverakis

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (1.94 MB)

Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts