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1.
Proc Natl Acad Sci U S A ; 121(2): e2313326120, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38165934

RESUMEN

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.


Asunto(s)
Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Piel/patología , Folículo Piloso
2.
Adv Skin Wound Care ; 35(4): 219-223, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35085122

RESUMEN

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.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Enzima Convertidora de Angiotensina 2/genética , Células Endoteliales , Humanos , Hibridación in Situ , Queratinocitos , ARN , SARS-CoV-2
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