Browse by author
Lookup NU author(s): Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 National Academy of Sciences. All rights reserved.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.
Author(s): Ganier C, Mazin P, Herrera-Oropez G, Du-Harpu X, Blakeley M, Gabriel J, Predeus AV, Cakir B, Prete M, Harun N, Darrigrand J-F, Haiser A, Wyles S, Shaw T, Teichmann SA, Haniffa M, Watt FM, Lynch MD
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Year: 2024
Volume: 121
Issue: 2
Print publication date: 09/01/2024
Online publication date: 02/01/2024
Acceptance date: 13/11/2023
Date deposited: 22/01/2024
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: https://doi.org/10.1073/pnas.2313326120
DOI: 10.1073/pnas.2313326120
Data Access Statement: The raw and processed datasets for scRNAseq and Visium ST generated in the current study are available on ArrayExpress under “E-MTAB-13085” (59) and “E-MTAB-13084” (60) accessions and an interactive tool to display and download scRNAseq, ST and ISS data is available at https://spatial-skin-atlas.cellgeni.sanger.ac.uk/ (32). Previously published data were analysed in this work (17, 19). All other data are included in the manuscript and/or SI Appendix.
PubMed id: 38165934
Altmetrics provided by Altmetric
