Large and Small Assembly: Combining Functional Macromolecules with Small Peptides to Control the Morphology of Skeletal Muscle Progenitor Cells

Generation of skeletal muscle cells with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in human myogenic specification. In this study, we characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ pluripotent stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ skeletal muscle progenitor cells, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each isolated cell population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using a knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitor cells. Our data revealed a new role of TWIST1 in human skeletal muscle progenitors, and we have established a foundation to identify transcriptional regulations of human myogenic ontogeny (online database can be accessed in http://www.myogenesis.net/).

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Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1480-x ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 4

Author(s):

Yusef Yousuf ◽

Andrea Datu ◽

Ben Barnes ◽

Saeid Amini-Nik ◽

Marc G. Jeschke

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Progenitor Cells ◽

Satellite Cells ◽

Muscle Wasting ◽

Burn Injury ◽

Metabolic Effects ◽

Metformin Treatment ◽

Muscle Catabolism ◽

Muscle Progenitor Cells

Abstract Background Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hyperglycemia but has also been shown to have a beneficial effect on stem cells after injury. We hypothesize that metformin administration will increase protein synthesis in the skeletal muscle by increasing the proliferation of muscle progenitor cells, thus mitigating muscle atrophy post-burn injury. Methods To determine whether metformin can attenuate muscle catabolism following burn injury, we utilized a 30% total burn surface area (TBSA) full-thickness scald burn in mice and compared burn injuries with and without metformin treatment. We examined the gastrocnemius muscle at 7 and 14 days post-burn injury. Results At 7 days, burn injury significantly reduced myofiber cross-sectional area (CSA) compared to sham, p < 0.05. Metformin treatment significantly attenuated muscle catabolism and preserved muscle CSA at the sham size. To investigate metformin’s effect on satellite cells (muscle progenitors), we examined changes in Pax7, a transcription factor regulating the proliferation of muscle progenitors. Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05. Moreover, through BrdU proliferation assay, we show that metformin treatment increased the proliferation of satellite cells at 7 days post-burn injury, p < 0.05. Conclusion In summary, metformin’s various metabolic effects and its modulation of stem cells make it an attractive alternative to mitigate burn-induced muscle wasting while also managing hyperglycemia.

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Numb Promotes an Increase in Skeletal Muscle Progenitor Cells in the Embryonic Somite

Stem Cells ◽

10.1002/stem.220 ◽

2009 ◽

Vol 27 (11) ◽

pp. 2769-2780 ◽

Cited By ~ 34

Author(s):

AurÃ©lie Jory ◽

Isabelle Le Roux ◽

Barbara Gayraud-Morel ◽

Pierre Rocheteau ◽

Michel Cohen-Tannoudji ◽

...

Keyword(s):

Skeletal Muscle ◽

Progenitor Cells ◽

Muscle Progenitor Cells

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Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration

Development ◽

10.1242/dev.122317 ◽

2015 ◽

Vol 142 (4) ◽

pp. 810-810 ◽

Cited By ~ 2

Author(s):

R. Ogawa ◽

Y. Ma ◽

M. Yamaguchi ◽

T. Ito ◽

Y. Watanabe ◽

...

Keyword(s):

Skeletal Muscle ◽

Progenitor Cells ◽

Muscle Regeneration ◽

Skeletal Muscle Regeneration ◽

Muscle Progenitor Cells

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The use of skeletal muscle extracellular matrix extract to study how an aging environment impacts muscle progenitor cells

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.553.5 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Matthew Michael Stern ◽

Regina L. Myers ◽

Shay L. Soker ◽

Stephen B. Kritchevsky ◽

Mark Van Dyke

Keyword(s):

Skeletal Muscle ◽

Extracellular Matrix ◽

Progenitor Cells ◽

Muscle Progenitor Cells

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Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

10.1101/2020.02.24.963777 ◽

2020 ◽

Author(s):

Hasan Abbas ◽

Lindsey A. Olivere ◽

Michael E. Padgett ◽

Cameron A. Schmidt ◽

Brian F. Gilmore ◽

...

Keyword(s):

Skeletal Muscle ◽

Progenitor Cells ◽

Satellite Cells ◽

Muscle Regeneration ◽

Ischemic Injury ◽

Limb Ischemia ◽

Normal Muscle ◽

Mouse Muscle ◽

Muscle Progenitor Cells ◽

Artery Disease

AbstractPeripheral artery disease (PAD) is nearly as common as coronary artery disease, but few effective treatments exist, and it is associated with significant morbidity and mortality. Although PAD studies have focused on the vascular response to ischemia, skeletal muscle cells play a critically important role in determining the phenotypic manifestation of PAD. Here, we demonstrate that genetic ablation of Pax7+ muscle progenitor cells (MPCs, or satellite cells) in a murine model of hind limb ischemia (HLI) resulted in a complete absence of normal muscle regeneration following ischemic injury, despite a lack of morphological or physiological changes in resting muscle. Compared to ischemic muscle of control mice (Pax7WT), the ischemic limb of Pax7-deficient mice (Pax7Δ) was unable to generate significant force 7- or 28-days after HLI in ex vivo force measurement studies. A dramatic increase in adipose infiltration was observed 28 days after HLI in Pax7Δ mice, which replaced functional muscle. To investigate the mechanism of this adipogenic change, mice with inhibition of fibro/adipogenic precursors (FAPs), another pool of MPCs, were subjected to HLI. Inhibition of FAPs decreased muscle adipose fat but increased fibrosis. MPCs cultured from mouse muscle tissue failed to form myotubes in vitro following depletion of satellite cells in vivo, and they displayed an increased propensity to differentiate into fat in adipogenic medium. Importantly, this phenotype was recapitulated in patients with critical limb ischemia (CLI), the most severe form of PAD. Skeletal muscle samples from CLI patients demonstrated an increase in adipose deposition in more ischemic regions of muscle, which corresponded with a decrease in the number of satellite cells in those regions. Collectively, these data demonstrate that Pax7+ MPCs are required for normal muscle regeneration after ischemic injury, and they suggest that targeting muscle regeneration may be an important therapeutic approach to prevent muscle degeneration in PAD.

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