Fibroblasts: Origins, definitions, and functions in health and disease

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

doi:10.1016/j.cell.2021.06.024

Cited by 393 publications

(284 citation statements)

References 196 publications

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“…We observed that the number of interactions between cell groups at 1dpi was mostly increased compared to the uninjured, while cell-cell communication at 3dpi and 7dpi exhibited a dynamic change with both increased and decreased interactions (Figure 3B). Interestingly, both outgoing signaling and incoming signaling of fibroblasts and astrocytes were consistently enhanced at 1dpi, 3dpi, and 7dpi compared to the uninjured, consistent with the known important role of fibroblasts in tissue repair (Plikus, et al, 2021) (Figure 3B and Supplementary Figure S2A).…”

Section: Comparison Analysis Predicts Wnt Signaling As a Predominant Signaling Change During Mouse Embryonic Skin Developmentsupporting

confidence: 77%

Identification of Intercellular Signaling Changes Across Conditions and Their Influence on Intracellular Signaling Response From Multiple Single-Cell Datasets

2021

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Identification of intercellular signaling changes across multiple single-cell RNA-sequencing (scRNA-seq) datasets as well as how intercellular communications affect intracellular transcription factors (TFs) to regulate target genes is crucial in understanding how distinct cell states respond to evolution, perturbations, and diseases. Here, we first generalized our previously developed tool CellChat, enabling flexible comparison analysis of cell–cell communication networks across any number of scRNA-seq datasets from interrelated biological conditions. This greatly facilitates the ready detection of signaling changes of cell–cell communication in response to any biological perturbations. We then investigated how intercellular communications affect intracellular signaling response by inferring a multiscale signaling network which bridges the intercellular communications at the population level and the cell state–specific intracellular signaling network at the molecular level. The latter is constructed by integrating receptor-TF interactions collected from public databases and TF-target gene regulations inferred from a network-regularized regression model. By applying our approaches to three scRNA-seq datasets from skin development, spinal cord injury, and COVID-19, we demonstrated the capability of our approaches in identifying the predominant signaling changes across conditions and the critical signaling mechanisms regulating target gene expression. Together, our work will facilitate the identification of both intercellular and intracellular dysregulated signaling mechanisms responsible for biological perturbations in diverse tissues.

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Section: Comparison Analysis Predicts Wnt Signaling As a Predominant Signaling Change During Mouse Embryonic Skin Developmentsupporting

confidence: 77%

Identification of Intercellular Signaling Changes Across Conditions and Their Influence on Intracellular Signaling Response From Multiple Single-Cell Datasets

2021

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“…Historically, the outstanding question in the fibrosis field has been the origin of the myofibroblasts responsible for the scarring of the tissue. Candidate cellular origins include the activation of tissue-resident fibroblasts, the differentiation from bone marrow precursors, and the trans-differentiation of epithelial, mesothelial, and endothelial cells, macrophages, pericytes, and adipocytes into myofibroblasts (Plikus et al, 2021).…”

Section: Emt Classification: Type II and Type Iii Revisitedmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition in Fibrosis: Concepts and Targeting Strategies

Lovisa

2021

Front. Pharmacol.

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The epithelial-to-mesenchymal transition (EMT), an embryonic program relaunched during wound healing and in pathological conditions such as fibrosis and cancer, continues to gain the attention of the research community, as testified by the exponential trend of publications since its discovery in the seventies. From the first description as a mesenchymal transformation, the concept of EMT has been substantially refined as an in-depth comprehension of its functional role has recently emerged thanks to the implementation of novel mouse models as well as the use of sophisticated mathematical modeling and bioinformatic analysis. Nevertheless, attempts to targeting EMT in fibrotic diseases are at their infancy and continue to pose several challenges. The aim of this mini review is to recapitulate the most recent concepts in the EMT field and to summarize the different strategies which have been exploited to target EMT in fibrotic disorders.

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“…The origin and functional diversities of fibroblasts attract increasing attention in the field (reviewed in [29][30][31]). However, the heterogeneity of fascial fibroblasts is relatively understudied.…”

Section: Composition Of Subcutaneous Fasciamentioning

confidence: 99%

Furnishing Wound Repair by the Subcutaneous Fascia

Jiang

Rinkevich

2021

IJMS

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Mammals rapidly heal wounds through fibrous connective tissue build up and tissue contraction. Recent findings from mouse attribute wound healing to physical mobilization of a fibroelastic connective tissue layer that resides beneath the skin, termed subcutaneous fascia or superficial fascia, into sites of injury. Fascial mobilization assembles diverse cell types and matrix components needed for rapid wound repair. These observations suggest that the factors directly affecting fascial mobility are responsible for chronic skin wounds and excessive skin scarring. In this review, we discuss the link between the fascia’s unique tissue anatomy, composition, biomechanical, and rheologic properties to its ability to mobilize its tissue assemblage. Fascia is thus at the forefront of tissue pathology and a better understanding of how it is mobilized may crystallize our view of wound healing alterations during aging, diabetes, and fibrous disease and create novel therapeutic strategies for wound repair.

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Fibroblasts: Origins, definitions, and functions in health and disease

Cited by 393 publications

References 196 publications

Identification of Intercellular Signaling Changes Across Conditions and Their Influence on Intracellular Signaling Response From Multiple Single-Cell Datasets

Identification of Intercellular Signaling Changes Across Conditions and Their Influence on Intracellular Signaling Response From Multiple Single-Cell Datasets

Epithelial-to-Mesenchymal Transition in Fibrosis: Concepts and Targeting Strategies

Furnishing Wound Repair by the Subcutaneous Fascia

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