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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Vydané v:	Journal of investigative dermatology Ročník 138; číslo 4; s. 811
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.04.2018
Predmet:	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
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Abstract	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.
AbstractList	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.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. 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.
Author	Philippeos, Christina Telerman, Stephanie B Driskell, Ryan R Lombardi, Giovanna Pisco, Angela O Soldin, Mark Shaw, Tanya J Watt, Fiona M Oulès, Bénédicte Lynch, Magnus D Elgueta, Raul
Author_xml	– sequence: 1 givenname: Christina surname: Philippeos fullname: Philippeos, Christina organization: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK – sequence: 2 givenname: Stephanie B surname: Telerman fullname: Telerman, Stephanie B organization: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK – sequence: 3 givenname: Bénédicte surname: Oulès fullname: Oulès, Bénédicte organization: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK – sequence: 4 givenname: Angela O surname: Pisco fullname: Pisco, Angela O organization: King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, UK – sequence: 5 givenname: Tanya J surname: Shaw fullname: Shaw, Tanya J organization: King's College London Centre for Molecular and Cellular Biology of Inflammation, London, UK – sequence: 6 givenname: Raul surname: Elgueta fullname: Elgueta, Raul organization: King's College London MRC Centre for Transplantation, Guy's Hospital, Great Maze Pond, London, UK – sequence: 7 givenname: Giovanna surname: Lombardi fullname: Lombardi, Giovanna organization: King's College London MRC Centre for Transplantation, Guy's Hospital, Great Maze Pond, London, UK – sequence: 8 givenname: Ryan R surname: Driskell fullname: Driskell, Ryan R organization: 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 – sequence: 9 givenname: Mark surname: Soldin fullname: Soldin, Mark organization: Department of Plastic and Reconstructive Surgery, St. George's National Health Service Trust, London, UK – sequence: 10 givenname: Magnus D surname: Lynch fullname: Lynch, Magnus D organization: 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 – sequence: 11 givenname: Fiona M surname: Watt fullname: Watt, Fiona M email: fiona.watt@kcl.ac.uk organization: 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
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29391249$$D View this record in MEDLINE/PubMed
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PublicationTitle	Journal of investigative dermatology
PublicationTitleAlternate	J Invest Dermatol
PublicationYear	2018
References	29579454 - J Invest Dermatol. 2018 Apr;138(4):729-730. doi: 10.1016/j.jid.2017.10.012.
References_xml	– reference: 29579454 - J Invest Dermatol. 2018 Apr;138(4):729-730. doi: 10.1016/j.jid.2017.10.012.
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Snippet	Previous studies have shown that mouse dermis is composed of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in...
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SubjectTerms	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
Title	Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations
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