In Utero Fetal Weight in Pigs Is Regulated by microRNAs and Their Target Genes

Impaired skeletal muscle growth in utero can result in reduced birth weight and poor carcass quality in pigs. Recently, we showed the role of microRNAs (miRNAs) and their target genes in prenatal skeletal muscle development and pathogenesis of intrauterine growth restriction (IUGR). In this study, we performed an integrative miRNA-mRNA transcriptomic analysis in longissimus dorsi muscle (LDM) of pig fetuses at 63 days post conception (dpc) to identify miRNAs and genes correlated to fetal weight. We found 13 miRNAs in LDM significantly correlated to fetal weight, including miR-140, miR-186, miR-101, miR-15, miR-24, miR-29, miR-449, miR-27, miR-142, miR-99, miR-181, miR-199, and miR-210. The expression of these miRNAs decreased with an increase in fetal weight. We also identified 1315 genes significantly correlated to fetal weight at 63 dpc, of which 135 genes were negatively correlated as well as identified as potential targets of the above-listed 13 miRNAs. These miRNAs and their target genes enriched pathways and biological processes important for fetal growth, development, and metabolism. These results indicate that the transcriptomic profile of skeletal muscle can be used to predict fetal weight, and miRNAs correlated to fetal weight can serve as potential biomarkers of prenatal fetal health and growth.

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Transcriptome analysis reveals the long intergenic noncoding RNAs contributed to skeletal muscle differences between Yorkshire and Tibetan pig

Scientific Reports ◽

10.1038/s41598-021-82126-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ziying Huang ◽

Qianqian Li ◽

Mengxun Li ◽

Changchun Li

Keyword(s):

Skeletal Muscle ◽

Noncoding Rna ◽

Muscle Development ◽

Target Genes ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Tibetan Pig ◽

The Difference ◽

Long Intergenic Noncoding Rna

AbstractThe difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of GO and KEGG analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.

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Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

Cells ◽

10.3390/cells10051007 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1007

Author(s):

Asghar Ali ◽

Eduard Murani ◽

Frieder Hadlich ◽

Xuan Liu ◽

Klaus Wimmers ◽

...

Keyword(s):

Skeletal Muscle ◽

Fetal Growth ◽

Intrauterine Growth Restriction ◽

Muscle Development ◽

Muscle Growth ◽

The Body ◽

Growth Restriction ◽

Economic Losses ◽

Biological Processes ◽

Intrauterine Growth

Intrauterine growth restriction (IUGR) occurs in 15–20% of pig neonates and poses huge economic losses to the pig industry. IUGR piglets have reduced skeletal muscle growth, which may persist after birth. Prenatal muscle growth is regulated by complex molecular pathways that are not well understood. MicroRNAs (miRNAs) have emerged as the main regulators of vital pathways and biological processes in the body. This study was designed to identify miRNA–mRNA networks regulating prenatal skeletal muscle development in pigs. We performed an integrative miRNA–mRNA transcriptomic analysis in longissimus dorsi muscle from IUGR fetuses and appropriate for gestational age (AGA) fetuses at 63 days post conception. Our data showed that 47 miRNAs and 3257 mRNAs were significantly upregulated, and six miRNAs and 477 mRNAs were significantly downregulated in IUGR compared to AGA fetuses. Moreover, 47 upregulated miRNAs were negatively correlated and can potentially target 326 downregulated genes, whereas six downregulated miRNAs were negatively correlated and can potentially target 1291 upregulated genes. These miRNA–mRNA networks showed enrichment in biological processes and pathways critical for fetal growth, development, and metabolism. The miRNA–mRNA networks identified in this study can potentially serve as indicators of prenatal fetal growth and development as well as postnatal carcass quality.

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Transcriptome Analysis Reveals the Long Intergenic Noncoding RNAs Contributed to Skeletal Muscle Differences between Yorkshire and Tibetan Pig

10.21203/rs.2.23862/v3 ◽

2020 ◽

Author(s):

Ziying Huang ◽

Qianqian Li ◽

Mengxun Li ◽

Changchun Li

Keyword(s):

Skeletal Muscle ◽

Noncoding Rna ◽

Muscle Development ◽

Target Genes ◽

Differential Expression Analysis ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Tibetan Pig ◽

The Difference

Abstract Background: The difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. Results: Through differential expression analysis, 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of Gene Ontology and pathway analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. Conclusions: In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.

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Transcriptome Analysis Reveals the Long Intergenic Noncoding RNAs Contributed to Skeletal Muscle Differences between Yorkshire and Tibetan Pig

10.21203/rs.2.23862/v1 ◽

2020 ◽

Author(s):

Ziying Huang ◽

Qianqian Li ◽

Mengxun Li ◽

Changchun Li

Keyword(s):

Skeletal Muscle ◽

Noncoding Rna ◽

Muscle Development ◽

Target Genes ◽

Differential Expression Analysis ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Tibetan Pig ◽

The Difference

Abstract Background The difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. Results Through differential expression analysis, 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of Gene Ontology and pathway analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. Conclusions In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.

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Transcriptome Analysis Reveals the Long Intergenic Noncoding RNAs Contributed to Skeletal Muscle Differences between Yorkshire and Tibetan Pig

10.21203/rs.2.23862/v2 ◽

2020 ◽

Author(s):

Ziying Huang ◽

Qianqian Li ◽

Mengxun Li ◽

Changchun Li

Keyword(s):

Skeletal Muscle ◽

Noncoding Rna ◽

Muscle Development ◽

Target Genes ◽

Differential Expression Analysis ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Tibetan Pig ◽

The Difference

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Maternal inflammation at midgestation impairs subsequent fetal myoblast function and skeletal muscle growth in rats, resulting in intrauterine growth restriction at term1

Translational Animal Science ◽

10.1093/tas/txz037 ◽

2019 ◽

Vol 3 (2) ◽

pp. 867-876 ◽

Cited By ~ 3

Author(s):

Caitlin N Cadaret ◽

Robert J Posont ◽

Kristin A Beede ◽

Hannah E Riley ◽

John Dustin Loy ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Glucose ◽

Intrauterine Growth Restriction ◽

Muscle Growth ◽

Maternal Blood ◽

Protein Catabolism ◽

Fetal Blood ◽

Intrauterine Growth ◽

Skeletal Muscle Growth ◽

Maternal Inflammation

Abstract Maternal inflammation induces intrauterine growth restriction (MI-IUGR) of the fetus, which compromises metabolic health in human offspring and reduces value in livestock. The objective of this study was to determine the effect of maternal inflammation at midgestation on fetal skeletal muscle growth and myoblast profiles at term. Pregnant Sprague-Dawley rats were injected daily with bacterial endotoxin (MI-IUGR) or saline (controls) from the 9th to the 11th day of gestational age (dGA; term = 21 dGA). At necropsy on dGA 20, average fetal mass and upper hindlimb cross-sectional areas were reduced (P < 0.05) in MI-IUGR fetuses compared with controls. MyoD+ and myf5+ myoblasts were less abundant (P < 0.05), and myogenin+ myoblasts were more abundant (P < 0.05) in MI-IUGR hindlimb skeletal muscle compared with controls, indicating precocious myoblast differentiation. Type I and Type II hindlimb muscle fibers were smaller (P < 0.05) in MI-IUGR fetuses than in controls, but fiber type proportions did not differ between experimental groups. Fetal blood plasma TNFα concentrations were below detectable amounts in both experimental groups, but skeletal muscle gene expression for the cytokine receptors TNFR1, IL6R, and FN14 was greater (P < 0.05) in MI-IUGR fetuses than controls, perhaps indicating enhanced sensitivity to these cytokines. Maternal blood glucose concentrations at term did not differ between experimental groups, but MI-IUGR fetal blood contained less (P < 0.05) glucose, cholesterol, and triglycerides. Fetal-to-maternal blood glucose ratios were also reduced (P < 0.05), which is indicative of placental insufficiency. Indicators of protein catabolism, including blood plasma urea nitrogen and creatine kinase, were greater (P < 0.05) in MI-IUGR fetuses than in controls. From these findings, we conclude that maternal inflammation at midgestation causes muscle-centric fetal programming that impairs myoblast function, increases protein catabolism, and reduces skeletal muscle growth near term. Fetal muscle sensitivity to inflammatory cytokines appeared to be enhanced after maternal inflammation, which may represent a mechanistic target for improving these outcomes in MI-IUGR fetuses.

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Dysregulation of Muscle-Specific MicroRNAs as Common Pathogenic Feature Associated with Muscle Atrophy in ALS, SMA and SBMA: Evidence from Animal Models and Human Patients

International Journal of Molecular Sciences ◽

10.3390/ijms22115673 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5673

Author(s):

Claudia Malacarne ◽

Mariarita Galbiati ◽

Eleonora Giagnorio ◽

Paola Cavalcante ◽

Franco Salerno ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Development ◽

Target Genes ◽

Muscular Atrophy ◽

Motor Neuron Diseases ◽

Muscle Involvement ◽

Mouse Muscle ◽

Noninvasive Biomarkers ◽

Muscle Impairment

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Due to the key role of muscle-specific microRNAs (myomiRs) in skeletal muscle development, by real-time PCR we investigated the expression of miR-206, miR-133a, miR-133b, and miR-1, and their target genes, in G93A-SOD1 ALS, Δ7SMA, and KI-SBMA mouse muscle during disease progression. Further, we analyzed their expression in serum of SOD1-mutated ALS, SMA, and SBMA patients, to demonstrate myomiR role as noninvasive biomarkers. Our data showed a dysregulation of myomiRs and their targets, in ALS, SMA, and SBMA mice, revealing a common pathogenic feature associated with muscle impairment. A similar myomiR signature was observed in patients’ sera. In particular, an up-regulation of miR-206 was identified in both mouse muscle and serum of human patients. Our overall findings highlight the role of myomiRs as promising biomarkers in ALS, SMA, and SBMA. Further investigations are needed to explore the potential of myomiRs as therapeutic targets for MND treatment.

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Analysis of long intergenic non-coding RNAs transcriptomic profiling in skeletal muscle growth during porcine embryonic development

Scientific Reports ◽

10.1038/s41598-021-94014-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenjuan Zhao ◽

Zijing Li ◽

Quan Liu ◽

Su Xie ◽

Mengxun Li ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Muscle Development ◽

Target Genes ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Protein Coding ◽

Development Stages ◽

Non Coding Rnas ◽

Embryonic Muscle

AbstractSkeletal muscle growth plays a critical role during porcine muscle development stages. Genome-wide transcriptome analysis reveals that long intergenic non-coding RNAs (lincRNAs) are implicated as crucial regulator involving in epigenetic regulation. However, comprehensive analysis of lincRNAs in embryonic muscle development stages remain still elusive. Here, we investigated the transcriptome profiles of Duroc embryonic muscle tissues from days 33, 65, and 90 of gestation using RNA-seq, and 228 putative lincRNAs were identified. Moreover, these lincRNAs exhibit the characteristics of shorter transcripts length, longer exons, less exon numbers and lower expression level compared with protein-coding transcripts. Expression profile analysis showed that a total of 120 lincRNAs and 2638 mRNAs were differentially expressed. In addition, we also performed quantitative trait locus (QTL) mapping analysis for differentially expressed lincRNAs (DE lincRNAs), 113 of 120 DE lincRNAs were localized on 2200 QTLs, we observed many QTLs involved in growth and meat quality traits. Furthermore, we predicted potential target genes of DE lincRNAs in cis or trans regulation. Gene ontology and pathway analysis reveals that potential targets of DE lincRNAs mostly were enriched in the processes and pathways related to tissue development, MAPK signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and insulin signaling pathway, which involved in skeletal muscle physiological functions. Based on cluster analysis, co-expression network analysis of DE lincRNAs and their potential target genes indicated that DE lincRNAs highly regulated protein-coding genes associated with skeletal muscle development. In this study, many of the DE lincRNAs may play essential roles in pig muscle growth and muscle mass. Our study provides crucial information for further exploring the molecular mechanisms of lincRNAs during skeletal muscle development.

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Analysis of Long Intergenic Non-Coding RNAs Transcriptomic Profiling in Skeletal Muscle Growth During Porcine Embryonic Development

10.21203/rs.3.rs-323967/v1 ◽

2021 ◽

Author(s):

Wenjuan Zhao ◽

Zijing Li ◽

Quan Liu ◽

Su Xie ◽

Mengxun Li ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Muscle Development ◽

Target Genes ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Protein Coding ◽

Development Stages ◽

Non Coding Rnas ◽

Embryonic Muscle

Abstract Skeletal muscle growth plays a critical role during porcine muscle development stages. Genome-wide transcriptome analysis reveals that thousands of long intergenic non-coding RNAs (lincRNAs) have been identified in various species and implicated as crucial regulator involving in epigenetic regulation. However, comprehensive analysis of lincRNAs in embryonic muscle development stages remain still elusive. Here, we investigated the transcriptome profiles of duroc embryonic muscle tissues from days 33, 65, and 90 of gestation using RNA-seq, there were 228 putative lincRNAs identified. Moreover, these lincRNAs exhibit the characteristics of shorter transcripts length, longer exons, less exon numbers and lower expression level compared with protein-coding transcripts. Differential expression analysis showed that a total of 91 lincRNAs and 2638 mRNAs were differentially expressed. In addition, we also performed quantitative trait locus (QTL) mapping analysis for DE lincRNAs, 113 of 120 DE lincRNAs were localized on 2200 QTLs, we observed many QTLs involved in growth and meat quality traits. Furthermore, we predicted potential target genes of DE lincRNAs in cis or trans regulation. Gene ontology and pathway analysis reveals that potential targets of DE lincRNAs mostly were enriched in the processes and pathways related to tissue development, MAPK signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and insulin signaling pathway, which involved in skeletal muscle physiological functions. Based on cluster analysis, a co-expression network analysis of DE lincRNAs and their potential target genes indicated that DE lincRNAs highly regulated protein-coding genes associated with skeletal muscle development. In this study, many of the DE lincRNAs identified may play essential roles in pig muscle growth and muscle mass. Our study provides crucial information for exploring further the molecular mechanisms of lincRNAs during skeletal muscle development.

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Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin

The Journal of Cell Biology ◽

10.1083/jcb.201109091 ◽

2012 ◽

Vol 197 (7) ◽

pp. 997-1008 ◽

Cited By ~ 103

Author(s):

Catherine E. Winbanks ◽

Kate L. Weeks ◽

Rachel E. Thomson ◽

Patricio V. Sepulveda ◽

Claudia Beyer ◽

...

Keyword(s):

Skeletal Muscle ◽

Intracellular Signaling ◽

Muscle Development ◽

Viral Vector ◽

Critical Role ◽

Muscle Growth ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Mediated Effects

Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed follistatin-induced Akt/mTOR/S6K signaling. Importantly, the regulation of Smad3- and mTOR-dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin. These findings identify a critical role of Smad3/Akt/mTOR/S6K/S6RP signaling in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms.

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