Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations

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 pr...

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Bibliographic Details
Published in:Journal of investigative dermatology Vol. 138; no. 4; p. 811
Main Authors: Philippeos, Christina, Telerman, Stephanie B, Oulès, Bénédicte, Pisco, Angela O, Shaw, Tanya J, Elgueta, Raul, Lombardi, Giovanna, Driskell, Ryan R, Soldin, Mark, Lynch, Magnus D, Watt, Fiona M
Format: Journal Article
Language:English
Published: United States 01.04.2018
Subjects:
Animals
Animals, Newborn
Cells, Cultured
Dermis - metabolism
Dermis - pathology
Extracellular Matrix - genetics
Extracellular Matrix - metabolism
Fibroblasts - metabolism
Fibroblasts - pathology
Flow Cytometry
Gene Expression Regulation, Developmental
Humans
Mice
Polymerase Chain Reaction
RNA - genetics
Signal Transduction
Wnt Proteins - biosynthesis
Wnt Proteins - genetics
Wound Healing - genetics
ISSN:1523-1747, 1523-1747
Online Access:Get more information
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Summary: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.
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ISSN:1523-1747
1523-1747
DOI:10.1016/j.jid.2018.01.016