Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.
Christina Philippeos, Stephanie B Telerman, Bénédicte Oulès, Angela O Pisco, Tanya J Shaw, Raul Elgueta, Giovanna Lombardi, Ryan R Driskell, Mark Soldin, Magnus D Lynch, Fiona M Watt
Author Information
- Christina Philippeos: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK.
- Stephanie B Telerman: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK.
- Bénédicte Oulès: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK.
- Angela O Pisco: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK.
- Tanya J Shaw: King's College London Centre for Molecular and Cellular Biology of Inflammation, London, UK.
- Raul Elgueta: King's College London MRC Centre for Transplantation, Guy's Hospital, Great Maze Pond, London, UK.
- Giovanna Lombardi: King's College London MRC Centre for Transplantation, Guy's Hospital, Great Maze Pond, London, UK.
- Ryan R Driskell: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK; School of Molecular Medicine, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
- Mark Soldin: Department of Plastic and Reconstructive Surgery, St. George's National Health Service Trust, London, UK.
- Magnus D Lynch: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK; St. John's Institute of Dermatology, Tower Wing, Guy's Hospital, Great Maze Pond, London, UK.
- Fiona M Watt: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK. Electronic address: fiona.watt@kcl.ac.uk.
Previous studies have shown that mouse dermis is composed of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in human skin, we 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 signaling, responsiveness to IFN-γ, and ability to support human epidermal reconstitution when introduced into decellularized 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.
Animals
Animals, Newborn
Cells, Cultured
Dermis
Extracellular Matrix
Fibroblasts
Flow Cytometry
Gene Expression Regulation, Developmental
Humans
Mice
Polymerase Chain Reaction
RNA
Signal Transduction
Wnt Proteins
Wound Healing
