ePrints

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

Lookup NU author(s): Professor Muzlifah Haniffa

Downloads

• Published version [.pdf]

Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 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.

Publication metadata

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

PubMed id: 38165934

Altmetrics

Share