Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

Clarisse Ganier*, Pavel Mazin, Gabriel Herrera-Oropez, Xinyi Du-Harpu, Matthew Blakeley, Jeyrroy Gabriel, Alexander V. Predeus, Batuhan Cakir, Martin Prete, Nasrat Harun, Jean Francois Darrigrand, Alexander Haiser, Saranya Wyles, Tanya Shaw, Sarah A. Teichmann, Muzlifah Haniffa, Fiona M. Watt*, Magnus D. Lynch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere2313326120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number2
DOIs
Publication statusPublished - 2024

Keywords

  • basal cell carcinoma
  • fibroblasts
  • human cell atlas
  • single cell RNA sequencing
  • skin

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