Multi-scale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma
Clarisse Ganier, Pavel Mazin, Gabriel Herrera-Oropeza, Xinyi Du-Harpur, Matthew Blakeley, Jeyrroy Gabriel, Alexander 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
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 multi-scale 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.
Datasets
1. BCC and Normal - scRNA-seq data
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Source data
https://cellxgene.cziscience.com/collections/34f12de7-c5e5-4813-a136-832677f98ac8
Alias names
E-MTAB-13085, PMID38165934, PMC10786309
Cite this study
Ganier, C., Mazin, P., Herrera-Oropeza, G., Du-Harpur, X., Blakeley, M., Gabriel, J., Predeus, A.V., Cakir, B., Prete, M., Harun, N. and Darrigrand, J.F., 2024. Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma. Proceedings of the National Academy of Sciences, 121(2), p.e2313326120. https://doi.org/10.1073%2Fpnas.2313326120