Wnt7a Suppresses Adipogenesis of Skeletal Muscle Mesenchymal Stem Cells and Fatty Infiltration Through the Alternative Wnt-Rho-YAP/TAZ Signaling Axis

Fu, Chengcheng; Guzmán-Seda, Mariana; Laudier, Damien M.; Han, Woojin M.

doi:10.1101/2022.06.30.498285

Cited by 4 publications

(3 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To probe for the underlying mechanism driving Vcam1+ FAP-promoted adipogenesis, we explored the RNA-seq profiles of Vcam1+ and Vcam1-FAPs for Wnt signaling, which has been reported to be a critical inhibitor of adipogenesis 33,34 . Indeed, Wnt signaling pathways were significantly downregulated in Vcam1+ FAPs compared to Vcam1-FAPs (Figure 4a).…”

Section: Sfrp1 Regulates Vcam1+ Fap Adipogenic Differentiationmentioning

confidence: 99%

“…We also observed decreased Wnt signaling in Vcam1+ FAPs. Canonical Wnt signaling is a well established inhibitor of adipogenesis 34 . In a murine muscular dystrophy model, Reggio et al demonstrated that the canonical Wnt/Gsk/B-catenin signaling axis inhibited FAP adipogenic differentiation 40 .…”

Section: Scrna-seq and Scatac-seq Identify Nr3c1 As A Candidate Cell-...mentioning

confidence: 99%

See 1 more Smart Citation

Vcam1+ Fibro-adipogenic Progenitors Mark Fatty Infiltration in Chronic Limb Threatening Ischemia

Dai,

Wan,

et al. 2024

Preprint

View full text Add to dashboard Cite

Skeletal muscle health and function is a critical determinant of clinical outcomes in patients with peripheral arterial disease (PAD). Herein, we identify fatty infiltration, the ectopic deposition of adipocytes in skeletal muscle, as a histological hallmark of end-stage PAD, also known as chronic limb threatening ischemia (CLTI). Leveraging single cell transcriptome mapping in mouse models of PAD, we identify a pro-adipogenic mesenchymal stromal cell population marked by expression of Vcam1 (termed Vcam1+ FAPs) that expands in the ischemic limb. Mechanistically, we identify Sfrp1 and Nr3c1 as regulators of Vcam1+ FAP adipogenic differentiation. Loss of Sfrp1 and Nr3c1 impair Vcam1+ FAP differentiation into adipocytesin vitro. Finally, we show that Vcam1+ FAPs are enriched in human CLTI patients. Collectively, our results identify a pro-adipogenic FAP subpopulation in CLTI patients and provide a potential therapeutic target for muscle regeneration in PAD.

show abstract

Section: Sfrp1 Regulates Vcam1+ Fap Adipogenic Differentiationmentioning

confidence: 99%

Section: Scrna-seq and Scatac-seq Identify Nr3c1 As A Candidate Cell-...mentioning

confidence: 99%

Vcam1+ Fibro-adipogenic Progenitors Mark Fatty Infiltration in Chronic Limb Threatening Ischemia

Dai,

Wan,

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Activation of the WNT5a/β-catenin signaling pathway can prevent the differentiation of FAPs into adipocytes, thereby inhibiting ectopic fat deposition in muscle ( Reggio et al., 2020 ). WNT7a also inhibits the differentiation of FAPs toward adipocytes and fatty infiltration through the WNT-Rho-YAP/TAZ signaling axis in a β-catenin-independent manner ( Fu et al., 2023 ). During skeletal muscle regeneration, activated FAPs secrete interleukin (IL)-6, which stimulates the proliferation and differentiation of SCs, thereby promoting skeletal muscle repair ( Joe et al., 2010 ).…”

Section: Introductionmentioning

confidence: 99%

MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration

Wang,

Yang,

et al. 2024

Stem Cell Reports

View full text Add to dashboard Cite

3D mechanical confinement directs muscle stem cell fate and function

Park,

Grey,

Mourkioti

et al. 2024

Preprint

View full text Add to dashboard Cite

Muscle stem cells (MuSCs) play a crucial role in skeletal muscle regeneration, residing in a niche that undergoes dimensional and mechanical changes throughout the regeneration process. This study investigates how three-dimensional (3D) confinement and stiffness encountered by MuSCs during the later stages of regeneration regulate their function, including stemness, activation, proliferation, and differentiation. We engineered an asymmetric 3D hydrogel bilayer platform with tunable physical constraints to mimic the regenerating MuSC niche. Our results demonstrate that increased 3D confinement maintains Pax7 expression, reduces MuSC activation and proliferation, inhibits differentiation, and is associated with smaller nuclear size and decreased H4K16ac levels, suggesting that mechanical confinement modulates both nuclear architecture and epigenetic regulation. MuSCs in unconfined two-dimensional (2D) environments exhibited larger nuclei and higher H4K16ac expression compared to those in more confined 3D conditions, leading to progressive activation, expansion, and myogenic commitment. This study highlights the importance of 3D mechanical cues in MuSC fate regulation, with 3D confinement acting as a mechanical brake on myogenic commitment, offering novel insights into the mechano-epigenetic mechanisms that govern MuSC behavior during muscle regeneration.

show abstract

Wnt7a Suppresses Adipogenesis of Skeletal Muscle Mesenchymal Stem Cells and Fatty Infiltration Through the Alternative Wnt-Rho-YAP/TAZ Signaling Axis

Cited by 4 publications

References 41 publications

Vcam1+ Fibro-adipogenic Progenitors Mark Fatty Infiltration in Chronic Limb Threatening Ischemia

Vcam1+ Fibro-adipogenic Progenitors Mark Fatty Infiltration in Chronic Limb Threatening Ischemia

MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration

3D mechanical confinement directs muscle stem cell fate and function

Contact Info

Product

Resources

About