Fibroblasts: Origins, Definitions, and Functions in Health and Disease

July 2021 in “ Cell ”

Maksim V. Plikus, Xiaojie Wang, Sarthak Sinha, Elvira Forte, Sean Thompson, Erica L. Herzog, Ryan R. Driskell, Nadia Rosenthal, Jeff Biernaskie, Valerie Horsley

fibroblasts tissue repair fibrosis inflammatory responses PDGF TGF-beta BMP skin fibrosis lung fibrosis myocardial inflammation fibroblast heterogeneity molecular mechanisms targeted therapies fibrotic diseases platelet-derived growth factor transforming growth factor-beta bone morphogenetic protein

Studysummary This review discusses the development, lineages, functions, and roles of fibroblasts in fibrosis across four organs, highlighting their capabilities in tissue repair and contributions to fibrotic disorders when aberrantly activated, but it reports no new experimental findings.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The document reviewed the origins, definitions, and functions of fibroblasts in health and disease, emphasizing their critical roles in tissue repair, fibrosis, and inflammatory responses. It discussed various signaling pathways, such as PDGF, TGF-beta, and BMP, that regulate fibroblast activity and differentiation. The review also highlighted the interactions between fibroblasts and other cell types, including inflammatory cells and adipocytes, and their contributions to conditions like skin fibrosis, lung fibrosis, and myocardial inflammation. Understanding fibroblast heterogeneity and the molecular mechanisms underlying their functions was emphasized as crucial for developing targeted therapies for fibrotic diseases.

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Single-Cell Transcriptomic Analysis of Small and Large Wounds Reveals the Distinct Spatial Organization of Regenerative Fibroblasts

research Single-Cell Transcriptomic Analysis of Small and Large Wounds Reveals the Distinct Spatial Organization of Regenerative Fibroblasts

35 citations , November 2020 in “Experimental Dermatology”

This study found that upper wound fibroblasts are crucial for hair follicle regeneration during wound healing and suggests that these cells, along with papillary fibroblasts, migrate within the wound.

research Distinct Regulatory Programs Control the Latent Regenerative Potential of Dermal Fibroblasts During Wound Healing

128 citations , August 2020 in “Cell stem cell”

In this study, researchers found that extrafollicular progenitors marked by Hic1 are the main contributors to reparative fibroblasts in wound repair, with potential to modulate healing outcomes through genetic and pharmacological interventions.

research Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair

124 citations , June 2020 in “Cell Stem Cell”

This study found that in mice, dermal adipocytes initiate inflammation and aid repair after skin injury by releasing lipids, suggesting a role in managing inflammatory diseases and impaired wound healing.

research Single-Cell Analysis Reveals Fibroblast Heterogeneity and Myeloid-Derived Adipocyte Progenitors in Murine Skin Wounds

301 citations , February 2019 in “Nature Communications”

In this study, researchers found that wound healing in mouse skin recruits diverse fibroblasts, including myeloid-derived cells, which contribute to regenerating adipocytes.

research Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta

96 citations , December 2018 in “Immunity”

This study found that inhibiting TGF-β receptors in adult dermal fibroblasts restored their function and increased resistance to Staphylococcus aureus infection by enhancing their adipogenic and antimicrobial capabilities.

research Hedgehog Stimulates Hair Follicle Neogenesis by Creating Inductive Dermis During Murine Skin Wound Healing

145 citations , November 2018 in “Nature Communications”

This study found that activating the Sonic hedgehog pathway in scarring wounds can remodel the dermis to promote hair follicle regeneration, highlighting a potential new approach to enhance healing.

research Wound Regeneration Deficit in Rats Correlates with Low Morphogenetic Potential and Distinct Transcriptome Profile of Epidermis

21 citations , January 2018 in “Journal of Investigative Dermatology”

This study found that large excisional wounds in rats across seven strains do not regenerate new hair follicles, unlike in mice, possibly due to differences in epidermal competence and transcriptional profiles.

research Adipocyte-Myofibroblast Transition as a Possible Pathophysiological Step in Androgenetic Alopecia

18 citations , May 2017 in “Experimental Dermatology”

This article discusses a potential link between adipocyte-myofibroblast transition and androgenetic alopecia, suggesting AMT may play a role in fibrosis associated with the condition but presents no new results.

research Platelet-Derived Growth Factor Signaling Modulates Adult Hair Follicle Dermal Stem Cell Maintenance and Self-Renewal

37 citations , April 2017 in “npj Regenerative Medicine”

This study found that platelet-derived growth factor signaling is crucial for maintaining the hair follicle dermal stem cell pool and supporting their regenerative capacity.

research Regeneration of Fat Cells from Myofibroblasts During Wound Healing

408 citations , January 2017 in “Science”

This study found that hair follicles in mice and humans can convert wound-related myofibroblasts into adipocytes, suggesting a potential pathway to reduce scar formation by activating BMP signaling.

research Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT Signaling Axis

106 citations , October 2016 in “Cell Stem Cell”

This study found that PDGFA is critical for the proliferation and maintenance of adipocyte stem cells in skin but not other white adipose tissues, highlighting unique regulatory mechanisms in different tissue depots.

research Hair Follicles’ Transit-Amplifying Cells Govern Concurrent Dermal Adipocyte Production Through Sonic Hedgehog

75 citations , October 2016 in “Genes & Development”

This study found that Sonic Hedgehog secreted by hair follicle transit-amplifying cells is essential for dermal adipogenesis and hair follicle growth by acting on adipocyte precursors.

Differential Expression Between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

research Differential Expression Between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

46 citations , April 2016 in “Journal of Investigative Dermatology”

This study suggests that down-regulation of vasculature-related genes in dermal papilla cells from balding scalps might contribute to the development of androgenetic alopecia.

research Inhibition of β-Catenin Signaling in Dermal Fibroblasts Enhances Hair Follicle Regeneration During Wound Healing

87 citations , January 2016 in “Development”

This study suggests that the postnatal loss of hair follicle formation in wounds may be due to elevated Wnt/β-catenin activation in the dermis, affecting fibroblast function in mice.

research A Guide to Studying Human Hair Follicle Cycling In Vivo

212 citations , September 2015 in “Journal of Investigative Dermatology”

This article presents a comprehensive guide for classifying human hair follicle cycle stages in vivo using scalp xenografts on immunocompromised mice, offering valuable resources for researchers in the field.

research An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin

173 citations , August 2015 in “Developmental cell”

This study characterizes gene expression patterns in embryonic hair follicle progenitors and their niche, identifying signaling pathways like axon guidance that may drive cellular rearrangements for hair follicle formation.

research Hair Follicle Dermal Stem Cells Regenerate the Dermal Sheath, Repopulate the Dermal Papilla, and Modulate Hair Type

184 citations , November 2014 in “Developmental Cell”

This study identifies a bipotent stem cell in adult hair follicles that self-renews and contributes to dermal sheath and papilla cell populations, potentially aiding hair regrowth after injury, disease, or aging.

research Distinct Fibroblast Lineages Determine Dermal Architecture in Skin Development and Repair

1235 citations , December 2013 in “Nature”

This study found that skin fibroblasts in mice arise from two distinct lineages which contribute differently to dermal structure and repair, impacting hair follicle formation during wound healing.

Microenvironmental Reprogramming by Three-Dimensional Culture Enables Dermal Papilla Cells to Induce De Novo Human Hair-Follicle Growth

research Microenvironmental Reprogramming by Three-Dimensional Culture Enables Dermal Papilla Cells to Induce De Novo Human Hair-Follicle Growth

256 citations , October 2013 in “Proceedings of the National Academy of Sciences of the United States of America”

This study found that altering cell culture conditions to form three-dimensional papilla spheroids can restore the ability of human dermal papilla cells to induce hair growth in adult skin.

Mesenchymal–Epithelial Interactions During Hair Follicle Morphogenesis and Cycling

research Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

990 citations , October 1999 in “Development”

This study found that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation in hair follicle development, indicating complex regulation in the skin.