Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations.

5 years ago

Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations.

Fiona M Watt, Magnus D Lynch, Angela O Pisco, Mark Soldin, Tanya J Shaw, Giovanna Lombardi, Raul Elgueta, Christina Philippeos, Bénédicte Oulès, Ryan R Driskell, Stephanie Telerman

Previous studies have shown that mouse dermis is comprised of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in human skin we have used a combination of comparative spatial transcriptional profiling of human and mouse dermis and single cell transcriptional profiling of human dermal fibroblasts. We show that there are at least four distinct fibroblast populations in adult human skin, not all of which are spatially segregated. We define markers permitting their isolation and show that although marker expression is lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signalling, responsiveness to IFNγ and ability to support human epidermal reconstitution when introduced into decellularised dermis. These findings suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications in wound healing and diseases characterized by excessive fibrosis.

Publisher URL: http://doi.org/10.1016/j.jid.2018.01.016

DOI: 10.1016/j.jid.2018.01.016