ORIGINAL INVESTIGATIONSAngiotensin-Converting Enzyme 2 Expression Is Detectable in Keratinocytes, Cutaneous Appendages, and Blood Vessels by Multiplex RNA In Situ HybridizationGanier, Clarisse PhD; Harun, Nasrat BSc; Peplow, Imogen BSc; Du-Harpur, Xinyi MBBChir; Arthurs, Callum BSc; Watt, Fiona M. PhD; Lynch, Magnus D. MA, DPhil, MRCS, MRCP Author Information At the Centre for Stem Cells and Regenerative Medicine, King’s College London, Guy’s Hospital, Great Maze Pond, London, UK, Clarisse Ganier, PhD, is Associate Researcher; Nasrat Harun, BSc, is Assistant Researcher; Imogen Peplow, BSc, is Assistant Researcher; Xinyi Du-Harpur, MBBChir, is PhD student; Callum Arthurs, BSc, is PhD student; Fiona M. Watt, PhD, is Director, Head of the Medical Research Council; and Magnus D. Lynch, MA, DPhil, MRCS, MRCP, is Consultant Dermatologist and Surgeon. Acknowledgment: The authors gratefully acknowledge financial support from the Wellcome Trust (211276/E/18/Z). The authors have disclosed no other financial relationships related to this article. Submitted March 30, 2021; accepted in revised form June 25, 2021; published online ahead of print January 26, 2022. Advances in Skin & Wound Care 35(4):p 219-223, April 2022. | DOI: 10.1097/01.ASW.0000819776.56007.18 Buy SDC Metrics Abstract OBJECTIVE The angiotensin-converting enzyme 2 (ACE2) receptor mediates uptake of SARS-CoV-2, the virus responsible for COVID-19. Previous work analyzing publicly available bulk RNA-sequencing data sets has shown the expression of ACE2 in human keratinocytes. This finding is potentially relevant for the etiology of COVID-19-associated rashes and might also suggest a possible entry mechanism for the SARS-CoV-2 virus. In this study, the authors examined the spatial localization of ACE2 mRNA in vivo. METHODS AND RESULTS The authors analyzed several publicly available single-cell RNA-sequencing data sets. They determined spatial localization of ACE2 mRNA using multiplex RNA in situ hybridization in human skin. CONCLUSIONS Both analyses supported ACE2 expression in keratinocytes and skin vasculature, which could reflect a potential cutaneous entry point for SARS-CoV-2, particularly in damaged or broken skin. Moreover, ACE2 expression in vascular endothelial cells may support direct, virally mediated mechanisms in the etiology of the chilblain-like acral eruption that is seen in patients with COVID-19. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.