Isolation, Culture, and Differentiation of Fibro/Adipogenic Progenitors (FAPs) from Skeletal Muscle

Judson, Robert N.; Low, Marcela; Eisner, Christine; Rossi, Fábio

doi:10.1007/978-1-4939-7283-8_7

Cited by 37 publications

(29 citation statements)

References 7 publications

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“…1a ). FAPs were isolated by fluorescence-activated cell sorting (FACS) from hindlimb muscles based on expression of established cell surface markers, as negative for Ter119, CD45, CD31, and α7 integrin and positive for CD34 and Sca-1 4 , 5 , 19 - 21 (Fig. 1a ).…”

Section: Resultsmentioning

confidence: 99%

“…We found that the relative levels of Tie2 expression resolve Tie2-expressing FAPs into two subpopulations, Tie2 low and Tie2 high subFAPs that show distinct dynamic profiles during muscle regeneration following acute injury or during neonatal muscle growth. The overlap in the gene expression profiles of all subFAPs (including common FAP surface markers, such as Sca1, Pdgfrα, and CD90) 4 , 11 , 21 , 38 together with the emergence of transcriptional signatures that discriminate the various subFAPs upon muscle perturbation suggest that subFAPs range through a spectrum of cell states that are in dynamic transition. SubFAPs are regulated by signals that also trigger SC expansion and differentiation into myofibers, either within the neonatal muscle growth or during adult life (i.e., muscle repair in response to acute injury).…”

Section: Discussionmentioning

confidence: 99%

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Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

et al. 2018

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Fibro-adipogenic progenitors (FAPs) are currently defined by their anatomical position, expression of non-specific membrane-associated proteins, and ability to adopt multiple lineages in vitro. Gene expression analysis at single-cell level reveals that FAPs undergo dynamic transitions through a spectrum of cell states that can be identified by differential expression levels of Tie2 and Vcam1. Different patterns of Vcam1-negative Tie2high or Tie2low and Tie2low/Vcam1-expressing FAPs are detected during neonatal myogenesis, response to acute injury and Duchenne Muscular Dystrophy (DMD). RNA sequencing analysis identified cell state-specific transcriptional profiles that predict functional interactions with satellite and inflammatory cells. In particular, Vcam1-expressing FAPs, which exhibit a pro-fibrotic expression profile, are transiently activated by acute injury in concomitance with the inflammatory response. Aberrant persistence of Vcam1-expressing FAPs is detected in DMD muscles or upon macrophage depletion, and is associated with muscle fibrosis, thereby revealing how disruption of inflammation-regulated FAPs dynamics leads to a pathogenic outcome.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

et al. 2018

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“…Tissue preparation for skeletal muscle and heart FAPs was performed mainly as described before (Contreras et al, 2019c; Judson et al, 2017; Soliman et al, 2019 preprint). One-step digestion of tissue for FAPs was performed mainly as described before with some modifications (Judson et al, 2017; Lemos et al, 2015). All the steps were performed on ice unless otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα⁺ fibroblasts

Contreras¹,

Soliman

Théret

et al. 2020

Preprint

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Mesenchymal stromal/stem cells (MSCs) are multipotent progenitors essential ororganogenesis, tissue homeostasis, regeneration, and scar formation. Tissue injury upregulates TGF-β signaling, which modulates myofibroblast fate, extracellular matrix remodeling, and fibrosis. However, the molecular determinants of MSCs differentiation and survival remain poorly understood. The canonical Wnt Tcf/Lef transcription factors regulate development and stemness, but the mechanisms by which injury-induced cues modulate their expression remain underexplored. Here, we studied the cell-specific gene expression of Tcf/Lef and, more specifically, we investigated whether damage-induced TGF-β impairs the expression and function of TCF7L2, using several models of MSCs, including skeletal muscle fibro-adipogenic progenitors. We show that Tcf/Lefs are differentially expressed and that TGF-β reduces the expression of TCF7L2 in MSCs but not in myoblasts. We also found that the ubiquitin-proteasome system regulates TCF7L2 proteostasis and participates in TGF-β-mediated TCF7L2 protein downregulation. Finally, we show that TGF-β requires HDACs activity to repress the expression of TCF7L2. Thus, our work found a novel interplay between TGF-β and Wnt canonical signaling cascades in PDGFRα+ fibroblasts and suggests that this mechanism could be targeted in tissue repa ir and regeneration.Summary statementTGF-β signaling suppresses the expression of the Wnt transcription factor TCF7L2 and compromises TCF7L2-dependent functions in tissue-resident PDGFRα+ fibroblasts.

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“…Mouse muscular PDGFRA þ cells also express other mesenchymal markers, such as mesenchymal intermediate filament, Vimentin, together with the well-discussed adipogenesis repressor, delta like non-canonical Notch ligand 1 (Dlk1, also known as preadipocyte factor 1 or Pref1) (Uezumi et al, 2010). Of note, Sca1 (Stem cells antigen 1)positive cells overlap with over 85% of PDGFRA þ cells in undamaged mouse muscle and up to 98% in injured muscles (Joe et al, 2010), and Sca1 is also commonly used to sort mouse FAPs (Fiore et al, 2016;Judson et al, 2017). However, a new study uncovered a subset of intramuscular Sca1 þ /PDGFRAcells within endothelial cells which derived from Myf5 þ progenitors in mice (Huang et al, 2014).…”

Section: Molecular Markers and Heterogeneity Of Fibro-adipogenic Progmentioning

confidence: 99%

Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals

Xiao

Yang

et al. 2020

Animal

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In the livestock industry, subcutaneous and visceral fat pads are considered as wastes, while intramuscular fat or marbling fat is essential for improving flavor and palatability of meat. Thus, strategies for optimizing fat deposition are needed. Intramuscular adipocytes provide sites for lipid deposition and marbling formation. In the present article, we addressed the origin and markers of intramuscular adipocyte progenitors – fibro-adipogenic progenitors (FAPs), as well as the latest progresses in mechanisms regulating the proliferation and differentiation of intramuscular FAPs. Finally, by targeting intramuscular FAPs, possible nutritional manipulations to improve marbling fat deposition are discussed. Despite recent progresses, the properties and regulation of intramuscular FAPs in livestock remain poorly understood and deserve further investigation.

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Isolation, Culture, and Differentiation of Fibro/Adipogenic Progenitors (FAPs) from Skeletal Muscle

Cited by 37 publications

References 7 publications

Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα⁺ fibroblasts

Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals

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Isolation, Culture, and Differentiation of Fibro/Adipogenic Progenitors (FAPs) from Skeletal Muscle

Cited by 37 publications

References 7 publications

Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα+ fibroblasts

Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals

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TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα⁺ fibroblasts