Fibroblast heterogeneity: implications for human disease

Lynch, Magnus; Watt, Fiona M.

doi:10.1172/jci93555

Cited by 344 publications

(302 citation statements)

References 145 publications

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“…In addition, we also describe several fibroblast subpopulations with distinct functional and spatial specifics. These findings provide an important extension of previous observations describing fibroblast heterogeneity, including the distinction of papillary and reticular fibroblasts (Driskell and Watt, 2015;Lynch and Watt, 2018;Sriram et al, 2015). More specifically, our results suggest the existence of four major dermal fibroblast populations: secretory-papillary fibroblasts, secretory-reticular fibroblasts, mesenchymal fibroblasts and pro-inflammatory fibroblasts.…”

Section: Discussionsupporting

confidence: 88%

“…Fibroblasts maintain various paracrine interactions with other skin cell types, as well as direct cell-cell interactions (Lynch and Watt, 2018;Sriram et al, 2015). For instance, their contacts along the dermal-epidermal junction with the epidermal stem and progenitor cells (EpSPCs) are key for proper epidermal homeostasis (Schumacher et al, 2014;Sriram et al, 2015;Taniguchi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming

Solé-Boldo

Raddatz

Schuetz

et al. 2019

Preprint

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Solé-Boldo et al.2 SummaryFibroblasts are the main dermal cell type and are essential for the architecture and function of human skin. Important differences have been described between fibroblasts localized in distinct dermal layers, and these cells are also known to perform varied functions. However, this phenomenon has not been analyzed comprehensively yet. Here we have used single-cell RNA sequencing to analyze >15,000 cells from a sun-protected area in young and old donors. Our results define four main fibroblast subpopulations that can be spatially localized and functionally distinguished. Importantly, intrinsic aging reduces this fibroblast 'priming', generates distinct expression patterns of skin aging-associated genes, and substantially reduces the interactions of dermal fibroblasts with other skin cell types. Our work thus provides comprehensive evidence for a functional specialization of human dermal fibroblasts and suggests that the age-related loss of fibroblast priming contributes to human skin aging.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming

Solé-Boldo

Raddatz

Schuetz

et al. 2019

Preprint

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“…Questions surrounding the origin of fibroblasts have been muddled by various findings that upend long‐held beliefs that they are phenotypically and functionally homogeneous . Numerous studies now suggest fibroblasts are heterogeneous in their origins, molecular markers, and functions, particularly during the pathological remodeling of organ tissue . It appears that distinct niches of fibroblasts engage or are recruited to various tissues in response to injury.…”

Section: Introductionmentioning

confidence: 99%

Origin and functional heterogeneity of fibroblasts

2020

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The inherent plasticity and resiliency of fibroblasts make this cell type a conventional tool for basic research. But where do they come from, are all fibroblasts the same, and how do they function in disease? The first fibroblast lineages in mammalian development emerge from the ooze of primary mesenchyme during gastrulation. They are cells that efficiently create and negotiate the extracellular matrix of the mesoderm in order to migrate and meet their developmental fate. Mature fibroblasts in epithelial tissues live in the interstitial spaces between basement membranes that spatially delimit complex organ structures. While the function of resident fibroblasts in healthy tissues is largely conjecture, the accumulation of fibroblasts in pathologic lesions offers insight into biologic mechanisms that control their function; fibroblasts are poised to coordinate fibrogenesis in tissue injury, neoplasia, and aging. Here, we examine the developmental origin and plasticity of fibroblasts, their molecular and functional definitions, the epigenetic control underlying their identity and activation, and the evolution of their immune regulatory functions. These topics are reviewed through the lens of fate mapping using genetically engineered mouse models and from the perspective of single‐cell RNA sequencing. Recent observations suggest dynamic and heterogeneous functions for fibroblasts that underscore their complex molecular signatures and utility in injured tissues.

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“…DF heterogeneity has been recognized for several decades. Some in-depth reviews of DF heterogeneity can be found in reports by Sorrell and Caplan (2004), Sriram et al (2015), and Lynch and Watt (2018). Two key features of hDF heterogeneity are their distinctive proliferative and profibrotic capacities (especially their ability to secrete collagen) (Sorrell and Caplan, 2004;Wang et al, 2008;Sriram et al, 2015).…”

Section: The Concept Of Df Heterogeneitymentioning

confidence: 99%

Utilizing Human Dermal Fibroblast Heterogeneity in Autologous Dermal Fibroblast Therapy: An Overcomplicated Strategy or a Promising Approach?

Zuo

Wei

Chen

2019

The Anatomical Record

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Although human dermal fibroblast heterogeneity has been acknowledged for several decades and a large body of in vitro studies has been performed with zonal dermal fibroblast, current autologous dermal fibroblast therapies do not reflect human dermal fibroblast heterogeneity. To determine if the utilization of human dermal fibroblast heterogeneity in autologous dermal fibroblast therapy is more of a translational perspective that may thus be more likely to make it to the clinic, this article critically reviews the previous studies on dermal fibroblast heterogeneity performed to date. We found that in vitro studies of human dermal fibroblast heterogeneity have run nearly parallel to the in vivo study of autologous dermal fibroblast therapy. Although several human to nude mice xenotransplantation experiments have been performed in different layers of human dermal fibroblast, their clinical significance remains to be considered. We conclude that there is still a great gap between basic experiments and the clinical employment of human dermal fibroblast heterogeneity. To overcome this, it is necessary to conduct clinical trials, which might be restricted by ethical issues. Alternatively, it might be easier to conduct in vivo studies in animal models. Based on our previous study of dermal fibroblast heterogeneity in pigs, we propose the use of pigs as a good animal model for dermal fibroblast heterogeneity. Time will show whether the utilization of human dermal fibroblast heterogeneity in autologous dermal fibroblast therapy is an overcomplicated strategy or a promising approach. Anat Rec, 302:2126–2131, 2019. © 2019 American Association for Anatomy

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Fibroblast heterogeneity: implications for human disease

Cited by 344 publications

References 145 publications

Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming

Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming

Origin and functional heterogeneity of fibroblasts

Utilizing Human Dermal Fibroblast Heterogeneity in Autologous Dermal Fibroblast Therapy: An Overcomplicated Strategy or a Promising Approach?

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