Age-related gene expression and DNA methylation changes in rhesus macaque

Zhou, Min; Zhang, Liang; Yang, Qiao; Yan, Chaochao; Jiang, Peng; Lan, Yue; Wang, Jiao; Tang, Ruixiang; He, Miao; Lei, Guanglun; Sun, Pan; Su, Na; Price, Megan; Li, Jing; Lin, Fen; Yue, Bisong; Fan, Zhenxin

doi:10.1016/j.ygeno.2020.09.021

Cited by 13 publications

(15 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Complement factor H ( CFH ) was recently found to regulate complement activation in the liver, which is associated with hepatocellular injury ( 33 ), but our results demonstrated that there was no significant difference in CFH expression between GBC and control tissues. F2 , known as coagulation factor II, encoding the prothrombin protein, was recently reported to be aberrantly methylated in old Chinese rhesus macaques, which is similar to our findings ( 34 ). HPX (hemagglutinin) is a plasma acute-phase glycoprotein produced by the liver that binds with high affinity to equimolar heme, and it can counteract cardiac heme toxicity such as that caused by oxidative stress, disruption of cardiac Ca 2+ homeostasis and contractile dysfunction ( 35 ).…”

Section: Discussionsupporting

confidence: 92%

Mining of RNA Methylation-Related Genes and Elucidation of Their Molecular Biology in Gallbladder Carcinoma

Yang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Gallbladder carcinoma (GBC), which has high invasion and metastasis risks, remains the most common biliary tract malignancy. Surgical resection for GBC is the only effective treatment, but most patients miss the opportunity for curative surgery because of a lack of timely diagnosis. The aim of this study was to identify and verify early candidate diagnostic and prognostic RNA methylation related genes for GBC via integrated transcriptome bioinformatics analysis. Lists of GBC-related genes and methylation-related genes were collected from public databases to screen differentially expressed genes (DEGs) by using the limma package and the RobustRankAggreg (RRA) package. The core genes were collected with batch effects corrected by the RRA algorithm through protein interaction network analysis, signaling pathway enrichment analysis and gene ranking. Four modules obtained from four public microarray datasets were found to be related to GBC, and FGA, F2, HAO1, CFH, PIPOX, ITIH4, GNMT, MAT1A, MTHFD1, HPX, CTH, EPHX2, HSD17B6, AKR1C4, CFHR3, ENNP1, and NAT2 were revealed to be potential hub genes involved in methylation-related pathways and bile metabolism-related pathways. Among these, FGA, CFH, F2, HPX, and PIPOX were predicted to be methylated genes in GBC, but POPIX had no modification sites for RNA methylation. Furthermore, survival analysis of TCGA (the Cancer Genome Atlas) database showed that six genes among the hub genes, FGA, CFH, ENPP1, CFHR3, ITIH4, and NAT2, were highly expressed and significantly correlated with worse prognosis. Gene correlation analysis revealed that the FGA was positively correlated with the ENPP1, NAT2, and CFHR3, while CFH was positively correlated with the NAT2, CFHR3, and FGA. In addition, the results of immunohistochemistry (IHC) showed that the expressions of FGA, F2, CFH, PIPOX, ITIH4, GNMT, MAT1A, MTHFD1, HPX, CFHR3, NAT2, and ENPP1 were higher in GBC tissues than that in control tissues. In conclusion, two genes, FGA and CFH, were identified as RNA methylation-related genes also involved in bile metabolism in GBC, which may be novel biomarkers to early diagnose and evaluate prognosis for GBC.

show abstract

Section: Discussionsupporting

confidence: 92%

Mining of RNA Methylation-Related Genes and Elucidation of Their Molecular Biology in Gallbladder Carcinoma

Yang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…CG methylation levels on a genome-wide scale, including the upstream, gene-body and downstream in the stomach ( Figure 6 A) and small intestine ( Figure 6 B) of giant panda, red panda and ferret, were calculated. Although CG methylation levels may not be very accurate due to a lack of region adjustment for overlapping genes, our results showed that the methylation patterns of giant panda, red panda and ferret were similar to those of other species [ 37 , 38 , 39 , 40 ]. In both tissues of three species, the methylation levels of 2000 bp upstream of the gene start site gradually decreased to the regions near the gene start site, which exhibited the lowest methylation levels in all of the regions.…”

Section: Resultsmentioning

confidence: 61%

Comparative Transcriptomics and Methylomics Reveal Adaptive Responses of Digestive and Metabolic Genes to Dietary Shift in Giant and Red Pandas

Shen

Jie

et al. 2022

Genes

Self Cite

View full text Add to dashboard Cite

Both the giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to the order Carnivora, but have changed their dietary habits to eating bamboo exclusively. The convergent evolution characteristics of their morphology, genome and gut flora have been found in the two pandas. However, the research on the convergent adaptation of their digestion and metabolism to the bamboo diet, mediated by the dietary shift of the two pandas at the gene-expression and epigenetic regulation levels, is still lacking. We therefore used RNA sequencing among five species (two pandas and three non-herbivore mammals) and bisulfite sequencing among three species (two pandas and a carnivore ferret) to sequence key digestion and metabolism tissues (stomach and small intestine). Our results provide evidence that the convergent differentially expressed genes (related to carbohydrate utilization, bile secretion, Lys and Arg metabolism, vitamin B12 utilization and cyanide detoxification) of the two pandas are adaptive responses to the bamboo diet containing low lipids, low Lys and Arg, low vitamin B12 and high cyanide. We also profiled the genome-wide methylome maps of giant panda, red panda and ferret, and the results indicated that the promoter methylation of the two pandas may regulate digestive and metabolic genes to adapt to sudden environmental changes, and then, transmit genetic information to future generations to evolve into bamboo eaters. Taken together, our study provides new insights into the molecular mechanisms of the dietary shift and the adaptation to a strict bamboo diet in both pandas using comparative transcriptomics and methylomics.

show abstract

“…As CRs exhibit similar molecular and phenotypic changes to humans during aging, they are considered an excellent model species for studying cardiovascular ( Zhou et al, 2020 ) and microbiota-associated human diseases ( Chen et al, 2018 ; Janiak et al, 2021 ). Currently, our understanding of how the oral and gut microbiomes change in aged CRs and how these changes affect host gene expression and physiology during aging remains limited.…”

Section: Discussionmentioning

confidence: 99%

“…However, given the distant evolutionary relationships between such species and humans, findings may not be directly transferable to human aging. In contrast, considering their close relationship to humans ( Gibbs et al, 2007 ) and similar anatomy, physiology, and behavior ( Lan et al, 2020 ; Yan et al, 2020 ), non-human primates, such as rhesus macaques ( Macaca mulatta , RMs), are well-suited animal models and have been successfully used in aging-related studies ( Mattison et al, 2017 ; Campisi et al, 2019 ; Zhou et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Multi-omics analysis reveals the host–microbe interactions in aged rhesus macaques

Xu¹,

Lan

Wang

et al. 2022

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host–microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host–microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.

show abstract

Age-related gene expression and DNA methylation changes in rhesus macaque

Cited by 13 publications

References 57 publications

Mining of RNA Methylation-Related Genes and Elucidation of Their Molecular Biology in Gallbladder Carcinoma

Mining of RNA Methylation-Related Genes and Elucidation of Their Molecular Biology in Gallbladder Carcinoma

Comparative Transcriptomics and Methylomics Reveal Adaptive Responses of Digestive and Metabolic Genes to Dietary Shift in Giant and Red Pandas

Multi-omics analysis reveals the host–microbe interactions in aged rhesus macaques

Contact Info

Product

Resources

About