myoblast differentiation
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2022 ◽  
Vol 21 (2) ◽  
pp. 496-503
Author(s):  
Hua-yun HUANG ◽  
Zhong LIANG ◽  
Long-zhou LIU ◽  
Chun-miao LI ◽  
Zhen-yang HUANG ◽  
...  

2022 ◽  
Vol 23 (2) ◽  
pp. 801
Author(s):  
Mai Thi Nguyen ◽  
Wan Lee

Skeletal myogenesis is essential for the maintenance of muscle quality and quantity, and impaired myogenesis is intimately associated with muscle wasting diseases. Although microRNA (miRNA) plays a crucial role in myogenesis and relates to muscle wasting in obesity, the molecular targets and roles of miRNAs modulated by saturated fatty acids (SFA) are largely unknown. In the present study, we investigated the role of miR-320-3p on the differentiation of myogenic progenitor cells. Palmitic acid (PA), the most abundant dietary SFA, suppressed myogenic factors expression and impaired differentiation in C2C12 myoblasts, and these effects were accompanied by CFL2 downregulation and miR-320-3p upregulation. In particular, miR-320-3p appeared to target CFL2 mRNA directly and suppress the expression of CFL2, an essential factor for filamentous actin (F-actin) depolymerization. Transfection of myoblasts with miR-320-3p mimic increased F-actin formation and nuclear translocation of Yes-associated protein 1 (YAP1), a key component of mechanotransduction. Furthermore, miR-320-3p mimic increased myoblast proliferation and markedly impeded the expression of MyoD and MyoG, consequently inhibiting myoblast differentiation. In conclusion, our current study highlights the role of miR-320-3p on CFL2 expression, YAP1 activation, and myoblast differentiation and suggests that PA-inducible miR-320-3p is a significant mediator of muscle wasting in obesity.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Shang-Ze Li ◽  
Ze-Yan Zhang ◽  
Jie Chen ◽  
Ming-You Dong ◽  
Xue-Hua Du ◽  
...  

AbstractSerum response factor (SRF) regulates differentiation and proliferation by binding to RhoA-actin-activated MKL or Ras-MAPK-activated ELK transcriptional coactivators, but the molecular mechanisms responsible for SRF regulation remain unclear. Here, we show that Nemo-like kinase (NLK) is required for the promotion of SRF/ELK signaling in human and mouse cells. NLK was found to interact with and phosphorylate SRF at serine residues 101/103, which in turn enhanced the association between SRF and ELK. The enhanced affinity of SRF/ELK antagonized the SRF/MKL pathway and inhibited mouse myoblast differentiation in vitro. In a skeletal muscle-specific Nlk conditional knockout mouse model, forming muscle myofibers underwent hypertrophic growth, resulting in an increased muscle and body mass phenotype. We propose that both phosphorylation of SRF by NLK and phosphorylation of ELKs by MAPK are required for RAS/ELK signaling, confirming the importance of this ancient pathway and identifying an important role for NLK in modulating muscle development in vivo.


Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 58
Author(s):  
Ke Xu ◽  
Hao Zhou ◽  
Chengxiao Han ◽  
Zhong Xu ◽  
Jinmei Ding ◽  
...  

In mammals, Myostatin (MSTN) is a known negative regulator of muscle growth and development, but its role in birds is poorly understood. To investigate the molecular mechanism of MSTN on muscle growth and development in chickens, we knocked out MSTN in chicken fetal myoblasts (CFMs) and sequenced the mRNA transcriptomes. The amplicon sequencing results show that the editing efficiency of the cells was 76%. The transcriptomic results showed that 296 differentially expressed genes were generated after down-regulation of MSTN, including angiotensin I converting enzyme (ACE), extracellular fatty acid-binding protein (EXFABP) and troponin T1, slow skeletal type (TNNT1). These genes are closely associated with myoblast differentiation, muscle growth and energy metabolism. Subsequent enrichment analysis showed that DEGs of CFMs were related to MAPK, P13K/AKT, and STAT3 signaling pathways. The MAPK and P13K/AKT signaling pathways are two of the three known signaling pathways involved in the biological effects of MSTN in mammals, and the STAT3 pathway is also significantly enriched in MSTN knock out chicken leg muscles. The results of this study will help to understand the possible molecular mechanism of MSTN regulating the early differentiation of CFMs and lay a foundation for further research on the molecular mechanism of MSTN involvement in muscle growth and development.


2021 ◽  
Vol 8 ◽  
Author(s):  
Dan Hao ◽  
Xiao Wang ◽  
Yu Yang ◽  
Bo Thomsen ◽  
Lars-Erik Holm ◽  
...  

Resveratrol (RSV) has been confirmed to benefit human health. Resveratrol supplemented in the feeds of animals improved pork, chicken, and duck meat qualities. In this study, we identified differentially expressed (DE) messenger RNAs (mRNAs) (n = 3,856) and microRNAs (miRNAs) (n = 93) for the weighted gene co-expression network analysis (WGCNA) to investigate the co-expressed DE mRNAs and DE miRNAs in the primary bovine myoblasts after RSV treatment. The mRNA results indicated that RSV treatments had high correlations with turquoise module (0.91, P-value = 0.01) and blue module (0.93, P-value < 0.01), while only the turquoise module (0.96, P-value < 0.01) was highly correlated with the treatment status using miRNA data. After biological enrichment analysis, the 2,579 DE genes in the turquoise module were significantly enriched in the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The top two GO terms were actin filament-based process (GO:0030029) and actin cytoskeleton organization (GO:0030036). The top two KEGG pathways were regulation of actin cytoskeleton (bta04810) and tight junction (bta04530). Then, we constructed the DE mRNA co-expression and DE miRNA co-expression networks in the turquoise module and the mRNA–miRNA targeting networks based on their co-expressions in the key module. In summary, the RSV-induced miRNAs participated in the co-expression networks that could affect mRNA expressions to regulate the primary myoblast differentiation. Our study provided a better understanding of the roles of RSV in inducing miRNA and of the characteristics of DE miRNAs in the key co-expressed module in regulation of mRNAs and revealed new candidate regulatory miRNAs and genes for the beef quality traits.


2021 ◽  
Vol 22 (24) ◽  
pp. 13615
Author(s):  
Lingye Chen ◽  
Fatemeh Hassani Nia ◽  
Tobias Stauber

Investigations on ion channels in muscle tissues have mainly focused on physiological muscle function and related disorders, but emerging evidence supports a critical role of ion channels and transporters in developmental processes, such as controlling the myogenic commitment of stem cells. In this review, we provide an overview of ion channels and transporters that influence skeletal muscle myoblast differentiation, cardiac differentiation from pluripotent stem cells, as well as vascular smooth muscle cell differentiation. We highlight examples of model organisms or patients with mutations in ion channels. Furthermore, a potential underlying molecular mechanism involving hyperpolarization of the resting membrane potential and a series of calcium signaling is discussed.


2021 ◽  
Vol 5 (3) ◽  
pp. e202101216
Author(s):  
Stephen Sakuma ◽  
Ethan YS Zhu ◽  
Marcela Raices ◽  
Pan Zhang ◽  
Rabi Murad ◽  
...  

Nuclear pore complexes, the channels connecting the nucleus with the cytoplasm, are built by multiple copies of ∼30 proteins called nucleoporins. Recent evidence has exposed that nucleoporins can play cell type-specific functions. Despite novel discoveries into the cellular functions of nucleoporins, their role in the regulation of mammalian tissue physiology remains mostly unexplored because of a limited number of nucleoporin mouse models. Here we show that ablation of Nup210/Gp210, a nucleoporin previously identified to play a role in myoblast differentiation and Zebrafish muscle maturation, is dispensable for skeletal muscle formation and growth in mice. We found that although primary satellite cells from Nup210 knockout mice can differentiate, these animals show delayed muscle repair after injury. Moreover, Nup210 knockout mice display an increased percentage of centrally nucleated fibers and abnormal fiber type distribution as they age. Muscle function experiments also exposed that Nup210 is required for muscle endurance during voluntary running. Our findings indicate that in mammals, Nup210 is important for the maintenance of skeletal muscle integrity and for proper muscle function providing novel insights into the in vivo roles of nuclear pore complex components.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chun Huang ◽  
Fei Ge ◽  
Xiaoming Ma ◽  
Rongfeng Dai ◽  
Renqing Dingkao ◽  
...  

Cattle-yak, as the hybrid offspring of cattle (Bos taurus) and yak (Bos grunniens), demonstrates obvious heterosis in production performance. Male hybrid sterility has been focused on for a long time; however, the mRNAs and non-coding RNAs related to muscle development as well as their regulatory networks remain unclear. The phenotypic data showed that the production performance (i.e., body weight, withers height, body length, and chest girth) of cattle-yak was significantly better than that of the yak, and the economic benefits of the cattle-yak were higher under the same feeding conditions. Then, we detected the expression profiles of the longissimus dorsi muscle of cattle-yak and yak to systematically reveal the molecular basis using the high-throughput sequencing technology. Here, 7,126 mRNAs, 791 lncRNAs, and 1,057 circRNAs were identified to be differentially expressed between cattle-yaks and yaks in the longissimus dorsi muscle. These mRNAs, lncRNA targeted genes, and circRNA host genes were significantly enriched in myoblast differentiation and some signaling pathways related to muscle development (such as HIF-1 signaling pathway and PI3K-Akt signaling pathway). We constructed a competing endogenous RNA (ceRNA) network and found that some non-coding RNAs differentially expressed may be involved in the regulation of muscle traits. Taken together, this study may be used as a reference tool to provide the molecular basis for studying muscle development.


Author(s):  
Xinran Yang ◽  
Jianfang Wang ◽  
Xinhao Ma ◽  
Jiawei Du ◽  
Chugang Mei ◽  
...  

N6-methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic mRNA, and it plays an important role in regulating gene expression. Previous studies have found that m6A methylation plays a role in mammalian skeletal muscle development. However, the effect of m6A on bovine skeletal myogenesis are still unclear. Here, we selected proliferating myoblasts (GM) and differentiated myotubes (on the 4th day of differentiation, DM) for m6A-seq and RNA-seq to explore the m6A methylation modification pattern during bovine skeletal myogenesis. m6A-seq analysis revealed that m6A methylation was an abundant modification of the mRNA in bovine myoblasts and myotubes. We scanned 5,691–8,094 m6A-modified transcripts, including 1,437 differentially methylated genes (DMGs). GO and KEGG analyses revealed that DMGs were primarily involved in transcriptional regulation and RNA metabolism, as well as insulin resistance and metabolic pathways related to muscle development. The combined analysis further identified 268 genes that had significant changes at both m6A and mRNA levels, suggesting that m6A modification may regulate myoblast differentiation by mediating the expression of these genes. Furthermore, we experimentally confirmed four genes related to myogenesis, including MYOZ2, TWIST1, KLF5 and MYOD1, with differential changes in both m6A and mRNA levels during bovine myoblast differentiation, indicating that they can be potential candidate targets for m6A regulation of skeletal myogenesis. Our results may provide new insight into molecular genetics and breeding of beef cattle, and provide a reference for investigating the mechanism of m6A regulating skeletal muscle development.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 689-689
Author(s):  
Ling Ruan ◽  
Mark Hamrick ◽  
Bharati Mendhe ◽  
Carlos Isales ◽  
William Hill ◽  
...  

Abstract We have recently shown that increased levels of reactive oxygen species (ROS) in aging skeletal muscle are associated with increased expression of the senescence-associated microRNA miR-34a-5p (miR-34a). The histone deacetylase Sirt1 is a validated target of miR-34a, and miR-34a expression is induced by the tumor suppressor p53 which is itself stimulated by ROS. Long noncoding RNAs (lncRNAs) are known to function as “sponges” for microRNAs, but the role of such competing endogenous RNAs (ceRNA) in muscle aging is not well understood. We therefore examined in skeletal muscles of young (4-6 mos) and aged (22-24) male and female mice the expression of several lncRNAs that are predicted to bind miR-34a-5p in silico and whose predicted binding has been validated experimentally. Results indicate a significant decrease in lncRNA MALAT1 expression with aging. MALAT1 is known to be highly expressed during the later stages of myoblast differentiation and myotube maturation. We therefore treated C2C12 cells at 48 hrs with hydrogen peroxide (10 uM) and examined changes in MALAT1 expression. MALAT1 was significantly decreased with H2O2 treatment, whereas miR-34a is increased in C2C12 cells after hydrogen peroxide exposure. Age-related muscle atrophy mediated by ROS may therefore result in part from related mechanisms involving miR-34a activity: an increase in miR-34a targeting Sirt1 resulting from p53 activation and an increase in miR-34a bioavailability resulting from a decline in miR-34a “sponging” due to ceRNA MALAT1 depletion. These findings suggest that therapeutic interventions increasing MALAT1 expression in muscle may potentially enhance the preservation of muscle mass with aging.


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