Faculty Opinions recommendation of Notch signaling rescues loss of satellite cells lacking pax7 and promotes brown adipogenic differentiation.

Abstract Numerous physiological and pathological processes are controlled by free fatty acids (FFAs), which act as a signaling molecule in mammals. We hypothesized that oleic acid (Ole) may stimulate the formation of satellite cell-derived intramuscular adipose tissue. The objective of the current study was to determine the effect of Ole on GPR43 and factors related to the adipogenic differentiation of bovine satellite cells. Bovine satellite cells were isolated from the semimembranosus of two 14-month-old crossbreed steers. The isolated muscle satellite cells were incubated in Dulbecco’s Modified Eagle’s Medium (DMEM) solution with 10% Fetal Bovine Serum. Upon reaching 80 to 90% confluence, the growth medium was replaced with differentiation medium composed of DMEM and 2% horse serum, 10μg/mL insulin, 10μg/mL hydrocortisone, 10μM ciglitizone, and 1×antibiotic-antimycotic with dose of: 0, 1, 10, 100, or 500 μM of oleic acid (Ole). Addition of Ole on BSC induced transdifferentiation of myogenic lineage into adipocyte-like cells which formed lipid droplets within cells. Use of 100 μM and 500 μM Ole doses tended to result in a greater (P < 0.1) amount of mRNA gene expression of C/EBPβ compared to all other doses. This might suppress myogenic differentiation. Expression of PPARγ was not altered (P > 0.1) by treatment. The addition of 100 μM and 500 μM upregulated (P < 0.05) mRNA gene expression of GPR43 and 100 μM of Ole increased protein level of GPR43 (P < 0.05) and phosphorylated AMPKα (P < 0.05).

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Uhrf1 governs the proliferation and differentiation of muscle satellite cells

10.1101/2021.04.08.439096 ◽

2021 ◽

Author(s):

Hiroshi Sakai ◽

Yuichiro Sawada ◽

Naohito Tokunaga ◽

So Nakagawa ◽

Iori Sakakibara ◽

...

Keyword(s):

Dna Methylation ◽

Notch Signaling ◽

Satellite Cells ◽

Ring Finger ◽

Dna Hypomethylation ◽

Myogenic Cells ◽

Muscle Stem Cells ◽

Proliferation And Differentiation ◽

Essential Form ◽

Methylation Patterns

DNA methylation is an essential form of epigenetic regulation responsible for cellular identity. In muscle stem cells, termed satellite cells, DNA methylation patterns are tightly regulated during differentiation. However, it is unclear how these DNA methylation patterns are maintained. We demonstrate that a key epigenetic regulator, ubiquitin like with PHD and RING finger domains 1 (Uhrf1), is activated in proliferating myogenic cells but not expressed in quiescent or differentiated myogenic cells in mice. Ablation of Uhrf1 in mouse satellite cells impairs their proliferation and differentiation, leading to failed muscle regeneration. Loss of Uhrf1 in satellite cells alters transcriptional programs, leading to DNA hypomethylation with activation of Cdkn1a and Notch signaling. Although down-regulation of Cdkn1a rescued proliferation but not differentiation, inhibition of Notch signaling rescued impaired differentiation of Uhrf1-deficient satellite cells. These findings point to Uhrf1 as a regulator of self-renewal and differentiation of satellite cells via genome-wide DNA methylation patterning.

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Adult stem cells derived from skeletal muscle — biology and potential

Open Life Sciences ◽

10.2478/s11535-013-0137-x ◽

2013 ◽

Vol 8 (3) ◽

pp. 215-225

Author(s):

Ľuboš Danišovič ◽

Štefan Polák ◽

Ján Vojtaššák

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Satellite Cells ◽

Adult Stem Cells ◽

Adipogenic Differentiation ◽

Biological Properties ◽

In Vitro Expansion ◽

Muscle Biology

AbstractSkeletal muscle contains at least two distinct populations of adult stem cells — satellite cells and multipotent muscle-derived stem cells. Monopotential satellite cells are located under the basal lamina of muscle fibers. They are capable of giving rise only to cells of myogenic lineage, which play an important role in the processes of muscle regeneration. Multipotent muscle-derived stem cells are considered to be predecessors of the satellite cells. Under proper conditions, both in vitro and in vivo, they undergo myogenic, cardiogenic, chondrogenic, osteogenic and adipogenic differentiation. The main purpose of the present article is to summarize current information about adult stem cells derived from skeletal muscle, and to discuss their isolation and in vitro expansion techniques, biological properties, as well as their potential for regenerative medicine.

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Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0210 ◽

2018 ◽

Vol 96 (3) ◽

pp. 342-348 ◽

Cited By ~ 9

Author(s):

K. Perepelina ◽

R. Dmitrieva ◽

E. Ignatieva ◽

A. Borodkina ◽

A. Kostareva ◽

...

Keyword(s):

Stem Cells ◽

Notch Signaling ◽

Cellular Differentiation ◽

Adipogenic Differentiation ◽

Lamin A ◽

Cellular Functions ◽

Gene Encoding ◽

Differentiated Cells ◽

Lmna Mutation ◽

Notch Activation

Lamins A and C are involved in many cellular functions, owing to its ability to bind chromatin and transcription factors and affect their properties. Mutations of the LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, the signaling pathways involved in interactions with lamins during cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in the adipogenic differentiation of mesenchymal stem cells. Notch was activated using lentiviral Notch intracellular domain. Activation of Notch was estimated through the expression of Notch-responsive genes by qPCR and by activation of a luciferase CSL-reporter construct. The effect of LMNA mutation on Notch activation and adipogenic differentiation was analyzed in cells bearing lentiviral LMNA WT or LMNA R482L. We show that, when Notch is activated, LMNA R482L contributes to down-regulation of Notch activation in undifferentiated and differentiated cells, and decreases adipogenic differentiation. Thus, lamin A/C interacts with Notch signaling, thereby influencing cellular differentiation, and point mutation in LMNA could halt this interaction.

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Inhibition of Notch Signaling Promotes the Adipogenic Differentiation of Mesenchymal Stem Cells Through Autophagy Activation and PTEN-PI3K/AKT/mTOR Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000430167 ◽

2015 ◽

Vol 36 (5) ◽

pp. 1991-2002 ◽

Cited By ~ 88

Author(s):

Bao-quan Song ◽

Ying Chi ◽

Xue Li ◽

Wen-jing Du ◽

Zhi-Bo Han ◽

...

Keyword(s):

Notch Signaling ◽

Cell Fate ◽

Adipogenic Differentiation ◽

Notch Signaling Pathway ◽

Mtor Pathway ◽

Cell Fate Decisions ◽

Autophagy Inhibitor ◽

Secretase Inhibitor ◽

Novel Target

Background: The Notch signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. This study was designed to determine the role of Notch signaling in adipogenic differentiation of human bone marrow derived MSCs (BM-MSCs). Methods: The Notch signaling was inhibited by the γ-secretase inhibitor N-[N-(3,5-difluor- ophenacetyl-L-alanyl)]-S-phenylglycine t-butylester (DAPT). The markers involving adipogenic differentiation of MSCs, the relative pathway PTEN-PI3K/Akt/mTOR and autophagy activation were then analyzed. Furthermore, the autophagy inhibitor chloroquine (CQ) and 3-methyladenine (3-MA) were used to study the role of autophagy in the DAPT-induced the adipogenic differentiation of MSCs. Results: We first confirmed the down -regulation of Notch gene expression during MSCs adipocyte differentiation, and showed that the inhibition of Notch signaling significantly enhanced adipogenic differentiation of MSCs. Furthermore, Notch inhibitor DAPT induced early autophagy by acting on PTEN-PI3K/Akt/mTOR pathway. The autophagy inhibitor CQ and 3-MA dramatically abolished the effects of DAPT-induced autophagy and adipogenic differentiation of MSCs. Conclusion: Our results indicate that inhibition of Notch signaling could promote MSCs adipogenesis mediated by autophagy involving PTEN-PI3K/Akt/mTOR pathway. Notch signaling could be a novel target for regulating the adipogenic differentiation of MSCs.

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Notch Signaling Regulates Muscle Stem Cell Homeostasis and Regeneration in a Teleost Fish

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.726281 ◽

2021 ◽

Vol 9 ◽

Author(s):

Sami H. A. Sultan ◽

Carlene Dyer ◽

Robert D. Knight

Keyword(s):

Stem Cell ◽

Notch Signaling ◽

Satellite Cells ◽

Muscle Regeneration ◽

Teleost Fish ◽

Proliferative Response ◽

Differential Sensitivity ◽

Muscle Stem Cell ◽

Larval Stages

Muscle regeneration is mediated by the activity of resident muscle satellite cells (muSCs) that express Pax7. In mouse Notch signaling regulates muSCs during quiescence and promotes muSC proliferation in regeneration. It is unclear if these roles of Notch in regulating muSC biology are conserved across vertebrates or are a mammalian specific feature. We have therefore investigated the role of Notch in regulating muSC homeostasis and regeneration in a teleost fish, the zebrafish. We have also tested whether muSCs show differential sensitivity to Notch during myotome development. In an absence of injury Notch is important for preventing muSC proliferation at the vertical myoseptum. In contrast, Notch signaling promotes proliferation and prevents differentiation in the context of injury. Notch is required for the proliferative response to injury at early and later larval stages, suggesting it plays a similar role in regulating muSCs at developing and adult stages. Our results reveal a conserved role for Notch signaling in regulating muSCs under homeostasis and for promoting proliferation during regeneration in teleost fish.

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Stage-specific effects of Notch activation during skeletal myogenesis

eLife ◽

10.7554/elife.17355 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 34

Author(s):

Pengpeng Bi ◽

Feng Yue ◽

Yusuke Sato ◽

Sara Wirbisky ◽

Weiyi Liu ◽

...

Keyword(s):

Notch Signaling ◽

Satellite Cells ◽

Muscle Growth ◽

Skeletal Myogenesis ◽

Specific Effects ◽

Myogenic Stem Cells ◽

Sequential Activation ◽

Cell Niche ◽

Multinucleated Myotubes ◽

Notch Activation

Skeletal myogenesis involves sequential activation, proliferation, self-renewal/differentiation and fusion of myogenic stem cells (satellite cells). Notch signaling is known to be essential for the maintenance of satellite cells, but its function in late-stage myogenesis, i.e. post-differentiation myocytes and post-fusion myotubes, is unknown. Using stage-specific Cre alleles, we uncovered distinct roles of Notch1 in mononucleated myocytes and multinucleated myotubes. Specifically, constitutive Notch1 activation dedifferentiates myocytes into Pax7 quiescent satellite cells, leading to severe defects in muscle growth and regeneration, and postnatal lethality. By contrast, myotube-specific Notch1 activation improves the regeneration and exercise performance of aged and dystrophic muscles. Mechanistically, Notch1 activation in myotubes upregulates the expression of Notch ligands, which modulate Notch signaling in the adjacent satellite cells to enhance their regenerative capacity. These results highlight context-dependent effects of Notch activation during myogenesis, and demonstrate that Notch1 activity improves myotube’s function as a stem cell niche.

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