In vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting that engrafted PSC-derived myogenic cells remodel their transcriptional signature upon interaction within the adult muscle environment. Here, we show that engrafted myogenic progenitors also remodel their metabolic state. Assessment of oxygen consumption revealed that exposure to the adult muscle environment promotes overt changes in mitochondrial bioenergetics, as shown by the substantial suppression of energy requirements in re-isolated iPax3 donor-derived satellite cells compared to their in vitro-generated progenitors. Mass spectrometry-based metabolomic profiling further confirmed the relationship of engrafted iPax3 donor-derived cells to adult satellite cells. The fact that in vitro-generated myogenic progenitors remodel their bioenergetic signature upon in vivo exposure to the adult muscle environment may have important implications for therapeutic applications.
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http://dx.doi.org/10.3390/cells13010076 | DOI Listing |
Cells
January 2025
Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea.
An actin-binding protein, known as Calponin 3 (CNN3), modulates the remodeling of the actin cytoskeleton, a fundamental process for the maintenance of skeletal muscle homeostasis. Although the roles of CNN3 in actin remodeling have been established, its biological significance in myoblast differentiation remains largely unknown. This study investigated the functional significance of CNN3 in myogenic differentiation, along with its effects on actin remodeling and mechanosensitive signaling in C2C12 myoblasts.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea.
Cortactin (CTTN) is an actin-binding protein regulating actin polymerization and stabilization, which are vital processes for maintaining skeletal muscle homeostasis. Despite the established function of CTTN in actin cytoskeletal dynamics, its role in the myogenic differentiation of progenitor cells remains largely unexplored. In this study, we investigated the role of CTTN in the myogenic differentiation of C2C12 myoblasts by analyzing its effects on actin cytoskeletal remodeling, myocardin-related transcription factor A (MRTFA) nuclear translocation, serum response factor (SRF) activation, expression of myogenic transcription factors, and myotube formation.
View Article and Find Full Text PDFBioengineering (Basel)
December 2024
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Muscle stem cells (MuSCs) are essential for skeletal muscle regeneration, influenced by a complex interplay of mechanical, biochemical, and molecular cues. Properties of the extracellular matrix (ECM) such as stiffness and alignment guide stem cell fate through mechanosensitive pathways, where forces like shear stress translate into biochemical signals, affecting cell behavior. Aging introduces senescence which disrupts the MuSC niche, leading to reduced regenerative capacity via epigenetic alterations and metabolic shifts.
View Article and Find Full Text PDFJ Adv Res
December 2024
College of Animal Science, Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, Shandong Agricultural University, Taian, China; College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China. Electronic address:
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, but it is absent in some mammals, including pigs. During development, BAT progenitors are derived from paired box 7 (Pax7)-expressing somitic mesodermal stem cells, which also give rise to skeletal muscle. However, the intrinsic mechanisms underlying the fate decisions between brown fat and muscle progenitors remain elusive across species.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Background: Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.
Methods: Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays.
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