RT Journal Article SR Electronic T1 Revisiting the significance of keratin expression in complex epithelia JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.07.27.501769 DO 10.1101/2022.07.27.501769 A1 Erez Cohen A1 Craig Johnson A1 Catherine J. Redmond A1 Raji R. Nair A1 Pierre A. Coulombe YR 2022 UL http://biorxiv.org/content/early/2022/07/29/2022.07.27.501769.abstract AB A large group of keratin genes (n=54 in the human genome) code for intermediate filament (IF)-forming proteins and show differential regulation in epithelial cells and tissues. Keratin expression can be highly informative about the type of epithelial tissue, differentiation status of constituent cells, and biological context (e.g., normal vs. diseased settings). The foundational principles underlying the use of keratin expression to gain insight about epithelial cells and tissues primarily originated in pioneering studies conducted in the 1980s. The recent emergence of single cell transcriptomics provides an opportunity to revisit these principles and gain new insight into epithelial biology. Re-analysis of single cell RNAseq data collected from human and mouse skin has confirmed long-held views regarding the quantitative importance and pairwise regulation of specific keratin genes in keratinocytes of surface epithelia. Further, such analyses confirm and extend the notion that changes in keratin gene expression occur gradually as progenitor keratinocytes commit to and undergo differentiation, and challenge the prevailing assumption that specific keratin combinations reflect a mitotic vs. a post-mitotic, differentiating state. Our findings provide a blueprint for similar analyses in other tissues, and warrant a more nuanced approach in the use of keratin genes as biomarkers in epithelia.Competing Interest StatementThe authors have declared no competing interest.