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BMC Genomics Jun 2024The skeletal muscle growth rate and body size of Tibetan pigs (TIB) are lower than Large white pigs (LW). However, the underlying genetic basis attributing to these...
BACKGROUND
The skeletal muscle growth rate and body size of Tibetan pigs (TIB) are lower than Large white pigs (LW). However, the underlying genetic basis attributing to these differences remains uncertain. To address this knowledge gap, the present study employed whole-genome sequencing of TIB (slow growth) and LW (fast growth) individuals, and integrated with existing NCBI sequencing datasets of TIB and LW individuals, enabling the identification of a comprehensive set of genetic variations for each breed. The specific and predominant SNPs in the TIB and LW populations were detected by using a cutoff value of 0.50 for SNP allele frequency and absolute allele frequency differences (△AF) between the TIB and LW populations.
RESULTS
A total of 21,767,938 SNPs were retrieved from 44 TIB and 29 LW genomes. The analysis detected 2,893,106 (13.29%) and 813,310 (3.74%) specific and predominant SNPs in the TIB and LW populations, and annotated to 24,560 genes. Further GO analysis revealed 291 genes involved in biological processes related to striated and/or skeletal muscle differentiation, proliferation, hypertrophy, regulation of striated muscle cell differentiation and proliferation, and myoblast differentiation and fusion. These 291 genes included crucial regulators of muscle cell determination, proliferation, differentiation, and hypertrophy, such as members of the Myogenic regulatory factors (MRF) (MYOD, MYF5, MYOG, MYF6) and Myocyte enhancer factor 2 (MEF2) (MEF2A, MEF2C, MEF2D) families, as well as muscle growth inhibitors (MSTN, ACVR1, and SMAD1); KEGG pathway analysis revealed 106 and 20 genes were found in muscle growth related positive and negative regulatory signaling pathways. Notably, genes critical for protein synthesis, such as MTOR, IGF1, IGF1R, IRS1, INSR, and RPS6KA6, were implicated in these pathways.
CONCLUSION
This study employed an effective methodology to rigorously identify the potential genes associated with skeletal muscle development. A substantial number of SNPs and genes that potentially play roles in the divergence observed in skeletal muscle growth between the TIB and LW breeds were identified. These findings offer valuable insights into the genetic underpinnings of skeletal muscle development and present opportunities for enhancing meat production through pig breeding.
Topics: Animals; Polymorphism, Single Nucleotide; Muscle, Skeletal; Swine; Gene Frequency; Muscle Development; Whole Genome Sequencing; Tibet; Genome
PubMed: 38862895
DOI: 10.1186/s12864-024-10508-7 -
Molecular Nutrition & Food Research Jun 2024Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with...
SCOPE
Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied.
METHODS AND RESULTS
This study finds that KMP (1, 10 µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation.
CONCLUSION
Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health.
PubMed: 38860356
DOI: 10.1002/mnfr.202300685 -
Frontiers in Cell and Developmental... 2024HDAC11 is an epigenetic repressor of gene transcription, acting through its deacetylase activity to remove functional acetyl groups from the lysine residues of histones...
HDAC11 is an epigenetic repressor of gene transcription, acting through its deacetylase activity to remove functional acetyl groups from the lysine residues of histones at genomic loci. It has been implicated in the regulation of different immune responses, metabolic activities, as well as cell cycle progression. Recent studies have also shed lights on the impact of HDAC11 on myogenic differentiation and muscle development, indicating that HDAC11 is important for histone deacetylation at the promoters to inhibit transcription of cell cycle related genes, thereby permitting myogenic activation at the onset of myoblast differentiation. Interestingly, the upstream networks of HDAC11 target genes are mainly associated with cell cycle regulators and the acetylation of histones at the HDAC11 target promoters appears to be residue specific. As such, selective inhibition, or activation of HDAC11 presents a potential therapeutic approach for targeting distinct epigenetic pathways in clinical applications.
PubMed: 38859964
DOI: 10.3389/fcell.2024.1368171 -
BMC Molecular and Cell Biology Jun 2024
PubMed: 38849754
DOI: 10.1186/s12860-024-00513-9 -
Botanical Studies Jun 2024The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past...
BACKGROUND
The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays.
RESULTS
Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium.
CONCLUSIONS
Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625.
PubMed: 38842634
DOI: 10.1186/s40529-024-00422-2 -
IScience Jun 2024The routine need for myonuclear turnover in skeletal muscle, together with more sporadic demands for hypertrophy and repair, are performed by resident muscle stem cells...
The routine need for myonuclear turnover in skeletal muscle, together with more sporadic demands for hypertrophy and repair, are performed by resident muscle stem cells called satellite cells. Muscular dystrophies are characterized by muscle wasting, stimulating chronic repair/regeneration by satellite cells. Here, we derived and validated transcriptomic signatures for satellite cells, myoblasts/myocytes, and myonuclei using publicly available murine single cell RNA-Sequencing data. Our signatures distinguished disease from control in transcriptomic data from several muscular dystrophies including facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy, and myotonic dystrophy type I. For FSHD, the expression of our gene signatures correlated with direct counts of satellite cells on muscle sections, as well as with increasing clinical and pathological severity. Thus, our gene signatures enable the investigation of myogenesis in bulk transcriptomic data from muscle biopsies. They also facilitate study of muscle regeneration in transcriptomic data from human muscle across health and disease.
PubMed: 38840844
DOI: 10.1016/j.isci.2024.109947 -
Current Sports Medicine Reports Jun 2024Muscle injury in sport results in significant lost time and potential for reinjury for athletes. Autologous blood product, namely, platelet-rich plasma (PRP), has been... (Review)
Review
Muscle injury in sport results in significant lost time and potential for reinjury for athletes. Autologous blood product, namely, platelet-rich plasma (PRP), has been investigated for possible augmentation of the treatment timeline with prevention of reinjury; however, conflicting results have been identified. A growing body of basic science and clinical literature is forming that supports the use of platelet-poor plasma (PPP) for muscle injury. The purpose of this study was to provide a background of the basic science of PRP versus PPP for muscle injury and to identify and review the clinical evidence for both autologous blood products, including the author's clinical experience utilizing the blood products. At the tissue level, PRP causes myoblast proliferation while PPP has led to myoblast induction, potentially identifying improved native muscle healing. Conflicting studies have been identified for the use of PRP for muscle injury. A growing body of positive results for PPP was identified, but high-quality comparative studies are needed.
Topics: Humans; Platelet-Rich Plasma; Athletic Injuries; Muscle, Skeletal; Wound Healing
PubMed: 38838685
DOI: 10.1249/JSR.0000000000001173 -
FASEB Journal : Official Publication of... Jun 2024Pyruvate kinase is a glycolytic enzyme that converts phosphoenolpyruvate and ADP into pyruvate and ATP. There are two genes that encode pyruvate kinase in vertebrates;...
Pyruvate kinase is a glycolytic enzyme that converts phosphoenolpyruvate and ADP into pyruvate and ATP. There are two genes that encode pyruvate kinase in vertebrates; Pkm and Pkl encode muscle- and liver/erythrocyte-specific forms, respectively. Each gene encodes two isoenzymes due to alternative splicing. Both muscle-specific enzymes, PKM1 and PKM2, function in glycolysis, but PKM2 also has been implicated in gene regulation due to its ability to phosphorylate histone 3 threonine 11 (H3T11) in cancer cells. Here, we examined the roles of PKM1 and PKM2 during myoblast differentiation. RNA-seq analysis revealed that PKM2 promotes the expression of Dpf2/Baf45d and Baf250a/Arid1A. DPF2 and BAF250a are subunits that identify a specific sub-family of the mammalian SWI/SNF (mSWI/SNF) of chromatin remodeling enzymes that is required for the activation of myogenic gene expression during differentiation. PKM2 also mediated the incorporation of DPF2 and BAF250a into the regulatory sequences controlling myogenic gene expression. PKM1 did not affect expression but was required for nuclear localization of DPF2. Additionally, PKM2 was required not only for the incorporation of phosphorylated H3T11 in myogenic promoters but also for the incorporation of phosphorylated H3T6 and H3T45 at myogenic promoters via regulation of AKT and protein kinase C isoforms that phosphorylate those amino acids. Our results identify multiple unique roles for PKM2 and a novel function for PKM1 in gene expression and chromatin regulation during myoblast differentiation.
Topics: Animals; Pyruvate Kinase; Mice; Cell Differentiation; Phosphorylation; Histones; Myoblasts; Transcription Factors; Thyroid Hormone-Binding Proteins; Humans; Chromosomal Proteins, Non-Histone; Thyroid Hormones; DNA-Binding Proteins; Isoenzymes
PubMed: 38837439
DOI: 10.1096/fj.202400784R -
Poultry Science May 2024Long-term intensive genetic selection has led to significant differences between broiler and layer chickens, which are evident during the embryonic period. Despite this,...
Long-term intensive genetic selection has led to significant differences between broiler and layer chickens, which are evident during the embryonic period. Despite this, there is a paucity of research on the genetic regulation of the initial formation of muscle fiber morphology in chick embryos. Embryonic d 17 (E17) is the key time point for myoblast fusion completion and muscle fiber morphology formation in chickens. This study aimed to explore the genetic regulatory mechanisms underlying the early muscle fiber morphology establishment in broiler chickens of Cornish (CC) and White Plymouth Rock (RR) and layer chickens of White Leghorn (WW) at E17 using the transcriptomic and chromatin accessibility sequencing of pectoral major muscles. The results showed that broiler chickens exhibited significant higher embryo weight and pectoral major muscle weight at E17 compared to layer chickens (P = 0.000). A total of 1,278, 1,248, and 892 differentially expressed genes (DEGs) of RNA-seq data were identified between CC vs. WW, RR vs. WW, and CC vs. RR, separately. All DEGs were combined for cluster analysis and they were divided into 6 clusters, including cluster 1 with higher expression in broilers and cluster 6 with higher expression in layers. DEGs in cluster 1 were enriched in terms related to macrophage activation (P = 0.002) and defense response to bacteria (P = 0.002), while DEGs in cluster 6 showed enrichment in protein-DNA complex (P = 0.003) and monooxygenase activity (P = 0.000). ATAC-seq data analysis identified a total of 38,603 peaks, with 13,051 peaks for CC, 18,780 peaks for RR, and 6,772 peaks for WW. Integrative analysis of transcriptomic and chromatin accessibility data revealed GOLM1, ISLR2, and TOPAZ1 were commonly upregulated genes in CC and RR. Furthermore, screening of all upregulated DEGs in cluster 1 from CC and RR identified GOLM1, ISLR2, and HNMT genes associated with neuroimmune functions and MYOM3 linked to muscle morphology development, showing significantly elevated expression in broiler chickens compared to layer chickens. These findings suggest active neural system connectivity during the initial formation of muscle fiber morphology in embryonic period, highlighting the early interaction between muscle fiber formation morphology and the nervous system. This study provides novel insights into late chick embryo development and lays a deeper foundation for further research.
PubMed: 38833745
DOI: 10.1016/j.psj.2024.103882 -
Tissue Engineering. Part A Jun 2024The fusion index is a key indicator for quantifying the differentiation of a myoblast population, which is often calculated manually. In addition to being...
The fusion index is a key indicator for quantifying the differentiation of a myoblast population, which is often calculated manually. In addition to being time-consuming, manual quantification is also error prone and subjective. Several software tools have been proposed for addressing these limitations but suffer from various drawbacks, including unintuitive interfaces and limited performance. In this study, we describe MyoFInDer, a Python-based program for the automated computation of the fusion index of skeletal muscle. At the core of MyoFInDer is a powerful artificial intelligence-based image segmentation model. MyoFInDer also determines the total nuclei count and the percentage of stained area and allows for manual verification and correction. MyoFInDer can reliably determine the fusion index, with a high correlation to manual counting. Compared with other tools, MyoFInDer stands out as it minimizes the interoperator variability, minimizes process time and displays the best correlation to manual counting. Therefore, it is a suitable choice for calculating fusion index in an automated way, and gives researchers access to the high performance and flexibility of a modern artificial intelligence model. As a free and open-source project, MyoFInDer can be modified or extended to meet specific needs.
PubMed: 38832871
DOI: 10.1089/ten.TEA.2024.0049