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Cited by 454Wound Healing and TreatmentsSingle-cell and spatial transcriptomicsHair Growth and Disorders

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

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Philippeos, Christina, Telerman, Stephanie B., Oulès, Bénédicte, Pisco, Angela O., Shaw, Tanya J., Elgueta, Raul, Lombardi, Giovanna, Driskell, Ryan R. +3 more·2018·Journal of Investigative Dermatology
DOI 10.1016/j.jid.2018.01.016PMC PMC5869055
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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.

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  • Fibroblasts coordinate the function of the immune system via production of chemokines and cytokines, with heterogeneity in cytokines produced by different fibroblasts.

    “coordinate the function of the immune system via the production of chemokines and cytokines, although it should be noted that there is heterogeneity in the cytokines produced by different fibroblasts16–20.”

    From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [19]

    The Results sections report different expression of the chemokine genes Cxcl1 and Cxcl12 in mouse fibroblast subpopulations and different expression of inflammatory mediators in cultured human fibroblast subpopulations (page unavailable). The Discussion also describes differential expression of immunoregulatory genes, but the paper does not establish that these fibroblasts coordinate immune-system function through production of chemokines and cytokines, or directly measure heterogeneity in cytokine production. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Overwhelming evidence points to a degree of specialization among CAFs, which may reflect the increasingly appreciated specialization of normal fibroblasts.

    “Overwhelming evidence now points to a degree of specialization among CAFs, which may reflect the increasingly appreciated specialization of normal fibroblasts19,50.”

    From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [19]

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Authors
Philippeos, C., Telerman, S. B., Oulès, B., Pisco, A. O., Shaw, T. J., Elgueta, R., Lombardi, G., Driskell, R. R., Soldin, M., Lynch, M. D., & Watt, F. M.
Affiliations
  • Guy's Hospital (GB)
  • King's College London (GB)
  • National Health Service (GB)
Corresponding author
Watt, Fiona M.
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2018-04
Volume
138
Issue
4
Pages
811-825
ISSN
0022-202X (ISSN-L)
DOI
10.1016/j.jid.2018.01.016
PMC
PMC5869055
OpenAlex
W2785713700
Cited by
454
References
3
Citations by year
2026: 46 · 2025: 46 · 2024: 63 · 2023: 45 · 2022: 68 · 2021: 68 · 2020: 62 · 2019: 38 · 2018: 18
FWCI
39.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • Wellcome Trust
  • King's College Hospital NHS Foundation Trust
  • National Institute for Health and Care Research (CL-2013-17-002)
  • Academy of Medical Sciences
  • King's College London
  • European Commission
  • Medical Research Council (MR/P018823/1, MR/K019732/2)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
Keywords
dermal fibroblasts, fibroblast heterogeneity, human skin, spatial transcriptomics, single-cell RNA sequencing, Wnt signaling, fibrosis, wound healing, fibroblast markers
MeSH terms
Animals, Animals, Newborn, Cells, Cultured, Extracellular Matrix, Fibroblasts, Flow Cytometry, Humans, RNA, Wound Healing, Signal Transduction, Polymerase Chain Reaction, Gene Expression Regulation, Developmental, Dermis, Wnt Proteins, Mice

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