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Summary: Optical coherence tomography (OCT) is a noninvasive optical imaging method that can generate high‐resolution en face and cross‐sectional images of the skin in vivo to a maximum depth of 2 mm. While OCT holds considerable potential for noninvasive diagnosis and disease monitoring, it is poorly understood by many dermatologists. Here we aim to equip the practising dermatologist with an understanding of the principles of skin OCT and the potential clinical indications. We begin with an introduction to the technology and discuss the different modalities of OCT including angiographic (dynamic) OCT, which can image cutaneous blood vessels at high resolution. Next we review clinical applications. OCT has been most extensively investigated in the diagnosis of keratinocyte carcinomas, particularly basal cell carcinoma. To date, OCT has not proven sufficiently accurate for the robust diagnosis of malignant melanoma; however, the evaluation of abnormal vasculature with angiographic OCT is an area of active investigation. OCT, and in particular angiographic OCT, also shows promise in monitoring the response to therapy of inflammatory dermatoses, such as psoriasis and connective tissues disease. We additionally discuss a potential role for artificial intelligence in improving the accuracy of interpretation of OCT imaging data. [ABSTRACT FROM AUTHOR]

Biologic therapies targeting the IL-23/IL-17 axis have transformed the treatment of psoriasis. However, the early mechanisms of action of these drugs remain poorly understood. Here, we perform longitudinal single-cell RNA-sequencing in affected individuals receiving IL-23 inhibitor therapy. By profiling skin at baseline, day 3 and day 14 of treatment, we demonstrate that IL-23 blockade causes marked gene expression shifts, with fibroblast and myeloid populations displaying the most extensive changes at day 3. We also identify a transient WNT5A+/IL24+ fibroblast state, which is only detectable in lesional skin. In-silico and in-vitro studies indicate that signals stemming from these WNT5A+/IL24+ fibroblasts upregulate multiple inflammatory genes in keratinocytes. Importantly, the abundance of WNT5A+/IL24+ fibroblasts is significantly reduced after treatment. This observation is validated in-silico, by deconvolution of multiple transcriptomic datasets, and experimentally, by RNA in-situ hybridization. These findings demonstrate that the evolution of inflammatory fibroblast states is a key feature of resolving psoriasis skin., (© 2024. The Author(s).)

Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN + subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community., Competing Interests: Competing interests statement:In the last 3 y, S.A.T. has been a remunerated Scientific Advisory Board member for GlaxoSmithKline, Qiagen, Foresite Labs, and is a co-founder and equity holder of TransitionBio. F.M.W. and M.D.L. are co-founders of Fibrodyne. F.M.W. and M.D.L. have filed two patents related to skin fibroblasts.

Stem cell renewal and differentiation are regulated by interactions with the niche. Although multiple cell populations have been identified in distinct anatomical compartments, little is known about niche-specific molecular factors. Using skin as a model system and combining single-cell RNA-seq data analysis, immunofluorescence, and transgenic mouse models, we show that the transmembrane protein embigin is specifically expressed in the sebaceous gland and that the number of embigin-expressing cells is negatively regulated by Wnt. The loss of embigin promotes exit from the progenitor compartment and progression toward differentiation, and also compromises lipid metabolism. Embigin modulates sebaceous niche architecture by affecting extracellular matrix organization and basolateral targeting of monocarboxylate transport. We discover through ligand screening that embigin is a direct fibronectin receptor, binding to the N-terminal fibronectin domain without impairing integrin function. Our results solve the long-standing question of how embigin regulates cell adhesion and demonstrate a mechanism that couples adhesion and metabolism., Competing Interests: Declaration of interests V.J. is currently an employee at Experimentica, Kuopio, 70210, Finland. K.M.D. is currently an employee at Orion Oyj, Espoo, 02200, Finland. A.M. is currently an employee at CN Bio Innovations Cambridge, CB40XL, UK., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.)