Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 138, Issue 4, Pages 811-825Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2018.01.016
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Funding
- UK Medical Research Council
- Wellcome Trust
- European Union (Gene2Skin Twinning Programme)
- Academy of Medical Sciences
- Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre (BRC) award
- King's College London
- King's College Hospital NHS Foundation Trust
- Medical Research Council [G1100073, MR/P018823/1, MR/K019732/2] Funding Source: researchfish
- National Institute for Health Research [CL-2013-17-002] Funding Source: researchfish
- MRC [G1100073, MR/P018823/1, MR/K019732/2] Funding Source: UKRI
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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-gamma, 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.
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