Author affiliations: a; bc; d; ef g h; i jnd k

• 成果类型: Article
• 署名作者: Ganier, Clarisse; Mazin, Pavel; Herrera-Oropeza, Gabriel; Du-Harpur, Xinyi; Blakeley, Matthew; Gabriel, Jeyrroy; Predeus, Alexander, V; Cakir, Batuhan; Prete, Martin; Harun, Nasrat; Darrigrand, Jean-Francois; Haiser, Alexander; Wyles, Saranya; Shaw, Tanya; Teichmann, Sarah A.; Haniffa, Muzlifah; Watt, Fiona M.; Lynch, Magnus D.
• 署名单位: Guy's & St Thomas' NHS Foundation Trust; University of London; King's College London; University of London; King's College London; Francis Crick Institute; Mayo Clinic; University of London; King's College London; University of Cambridge; Newcastle University - UK; Newcastle Upon Tyne Hospitals NHS Foundation Trust; European Molecular Biology Laboratory (EMBL); University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15441
• DOI: 10.1073/pnas.2313326120
• 发表日期: 2024-01-09
• 关键词: basal-cell carcinoma; hair follicle; mouse skin; stem-cells; fibroblasts; DYNAMICS; GROWTH; cancer; tissue; tumors

摘要

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.