Significance of stress keratin expression in normal and diseased epithelia

Erez Cohen; Craig N Johnson; Rachael Wasikowski; Allison C Billi; Lam C Tsoi; J Michelle Kahlenberg; Johann E Gudjonsson; Pierre A Coulombe

doi:10.1016/j.isci.2024.108805

Significance of stress keratin expression in normal and diseased epithelia

iScience. 2024 Jan 5;27(2):108805. doi: 10.1016/j.isci.2024.108805. eCollection 2024 Feb 16.

Authors

Erez Cohen¹, Craig N Johnson¹, Rachael Wasikowski², Allison C Billi², Lam C Tsoi², J Michelle Kahlenberg^{2

3}, Johann E Gudjonsson^{2

3}, Pierre A Coulombe^{1

2

4}

Affiliations

¹ Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
² Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³ Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
⁴ Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.

Abstract

A group of keratin intermediate filament genes, the type II KRT6A-C and type I KRT16 and KRT17, are deemed stress responsive as they are induced in keratinocytes of surface epithelia in response to environmental stressors, in skin disorders (e.g., psoriasis) and in carcinomas. Monitoring stress keratins is widely used to identify keratinocytes in an activated state. Here, we analyze single-cell transcriptomic data from healthy and diseased human skin to explore the properties of stress keratins. Relative to keratins occurring in healthy skin, stress-induced keratins are expressed at lower levels and show lesser type I-type II pairwise regulation. Stress keratins do not "replace" the keratins expressed during normal differentiation nor reflect cellular proliferation. Instead, stress keratins are consistently co-regulated with genes with roles in differentiation, inflammation, and/or activation of innate immunity at the single-cell level. These findings provide a roadmap toward explaining the broad diversity and contextual regulation of keratins.

Keywords: Biological sciences; Dermatology; Immunology; Transcriptomics;.

Abstract

Grants and funding