Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles

Camps, J.; Breuls, Natacha; Sifrim, Alejandro; Giarratana, Nefele; Corvelyn, Marlies; Danti, Laura; Grosemans, Hanne; Vanuytven, Sebastiaan; Thiry, Irina; Belicchi, M.; Meregalli, Mirella; Platko, Khrystyna; MacDonald, Melissa E.; Austin, Richard C.; Gijsbers, Rik; Cossu, Giulio; Torrente, Yvan; Voet, Thierry; Sampaolesi, Maurilio

doi:10.1016/j.celrep.2020.107597

Cited by 74 publications

(76 citation statements)

References 68 publications

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“…Finally, while the inhibitory effect of GDF10 has been previously demonstrated in the context of adipogenesis in Areg-like/CD142+ muscle-resident stromal cells (Camps et al, 2020) as well as in differentiating 3T3-L1 cells (Hino et al, 2012), we found that inactivating Gdf10 in Aregs did not majorly interfere with their inhibitory activity towards other ASPCs.…”

Section: Discussionsupporting

confidence: 46%

“…These results recapitulate CD142+ ASPCs’ previously reported capacity to inhibit adipogenesis through paracrine signalling (Schwalie et al , 2018). Together with a recent, independent report showing a comparable capacity of CD142+ stromal cells in muscle (Camps et al , 2020), we therefore decided to reintroduce the original “Adipogenesis regulators” (Aregs) nomenclature to conceptually define CD142+ ASPCs.…”

Section: Resultsmentioning

confidence: 99%

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Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling

Zachara

et al. 2021

Preprint

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Adipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations: Dpp4+ stem-like cells, Aoc3+ pre-adipocyte-like cells, and the enigmatic CD142+ cells. A great challenge now is to functionally characterize these distinct ASPC populations. Here, we focus on CD142+ ASPCs since discrepant properties have been assigned to this subpopulation, from adipogenic to non- and even anti-adipogenic. To address these inconsistencies, we comprehensively characterized mammalian subcutaneous CD142+ ASPCs across various sampling conditions. Our findings demonstrate that CD142+ ASPCs exhibit high molecular and phenotypic robustness, firmly supporting their non- and anti-adipogenic properties. However, these properties emerge in an age-dependent manner, revealing surprising temporal CD142+ ASPC behavioural alterations. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142- ASPCs into a non-adipogenic, Areg-like one.

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Section: Discussionsupporting

confidence: 46%

Section: Resultsmentioning

confidence: 99%

Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling

Zachara

et al. 2021

Preprint

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“…Given the paracrine action of the TGF-β superfamily and preferential expression of Bmp3b in muscle-resident PDGFRa + cells, Bmp3b produced in the muscle-resident PDGFRa + cells may be responsible for muscle maintenance.Previous studies have also shown the beneficial function of Bmp3b by demonstrating its anti-adipogenic action, metabolically favorable influence on obesity(27), and a neuroprotective role following stroke(37). Recent single-cell RNA-Seq analysis of skeletal muscle also confirmed the anti-adipogenic role of Bmp3b(38).Notably, Bmp3b expression was decreased during aging in both mice and humans, whereas its administration to aged mice reversed certain phenotypes of sarcopenia,including the improvement of muscle function and mass. BMP3B-treated aged mice showed increased energy expenditure during the light period without the gain of locomotion activity.…”

mentioning

confidence: 82%

Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia

Uezumi¹,

Ikemoto-Uezumi²,

Zhou³

et al. 2021

Journal of Clinical Investigation

116

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“…Our previous study reported expression of CD82 in both quiescent and activated human satellite cells, with cells positive for CD82 exhibiting strong myogenic activity both in vitro and in vivo. Recent single cell RNA seq studies have also confirmed robust CD82 expression in mouse satellite cells [18,19]. In hematopoietic stem cells, CD82 expression is typically indicative of quiescence; thus, CD82 loss of function leads to over-proliferation of cells [20,21].…”

Section: Introductionmentioning

confidence: 91%

Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function

et al. 2020

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Background Tetraspanins are a family of proteins known to assemble protein complexes at the cell membrane. They are thought to play diverse cellular functions in tissues by modifying protein-binding partners, thus bringing complexity and diversity in their regulatory networks. Previously, we identified the tetraspanin KAI/CD82 as a prospective marker for human muscle stem cells. CD82 expression appeared decreased in human Duchenne muscular dystrophy (DMD) muscle, suggesting a functional link to muscular dystrophy, yet whether this decrease is a consequence of dystrophic pathology or a compensatory mechanism in an attempt to rescue muscle from degeneration is currently unknown. Methods We studied the consequences of loss of CD82 expression in normal and dystrophic skeletal muscle and examined the dysregulation of downstream functions in mice aged up to 1 year. Results Expression of CD82 is important to sustain satellite cell activation, as in its absence there is decreased cell proliferation and less efficient repair of injured muscle. Loss of CD82 in dystrophic muscle leads to a worsened phenotype compared to control dystrophic mice, with decreased pulmonary function, myofiber size, and muscle strength. Mechanistically, decreased myofiber size in CD82−/− dystrophic mice is not due to altered PTEN/AKT signaling, although increased phosphorylation of mTOR at Ser2448 was observed. Conclusion Basal CD82 expression is important to dystrophic muscle, as its loss leads to significantly weakened myofibers and impaired muscle function, accompanied by decreased satellite cell activity that is unable to protect and repair myofiber damage.

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Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles

Cited by 74 publications

References 68 publications

Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling

Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling

Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia

Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function

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