scholarly journals Gene expression profiling of the left ventricles in a rat model of intrinsic aerobic running capacity

2005 ◽  
Vol 23 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Soon Jin Lee ◽  
Justin A. Ways ◽  
John C. Barbato ◽  
David Essig ◽  
Krista Pettee ◽  
...  

Our previous work found DA rats superior for intrinsic aerobic running capacity (ARC) and several cardiac function indexes compared with Copenhagen (COP) rats, and identified ARC quantitative trait loci (QTLs) on rat chromosomes 16 (RNO16) and 3 (RNO3). The purpose of this study was to use these inbred rat strains as a genetic substrate for differential cardiac gene expression to identify candidate genes for the observed ARC QTLs. RNA expression was examined globally in left ventricles of 15-wk-old DA, F1(COP × DA), and COP rats using microarrays to identify candidate genes for ARC QTLs. We identified 199 differentially expressed probe sets and determined their chromosomal locations. Six differentially expressed genes and expressed sequence tags (ESTs) mapped near ARC QTL regions, including PDZ and LIM domain 3 ( Pdlim3). Differential expression of these genes/ESTs was confirmed by quantitative RT-PCR. The Ingenuity Pathways program identified 13 biological networks containing 50 (of the 199) differentially expressed probe sets and 85 additional genes. Four of these eighty-five genes mapped near ARC QTL-containing regions, including insulin receptor substrate 2 ( Irs2) and acyl-CoA sythetase long-chain family member 1 ( Acsl1). Most (148/199) differentially expressed probe sets showed left ventricular expression patterns consistent with the alleles exerting additive effects, i.e., F1(COP × DA) rat RNA expression was intermediate between DA and COP rats. This study identified several potential ARC QTL candidate genes and molecular networks, one of them related to energy expenditure involving Pik3r1 mRNA expression that may, in part, explain the observed strain differences in ARC and cardiac performance.

2021 ◽  
Vol 12 ◽  
Author(s):  
Taraswi Mitra Ghosh ◽  
Jason White ◽  
Joshua Davis ◽  
Suman Mazumder ◽  
Teeratas Kansom ◽  
...  

Repetitive, low-dose (metronomic; METRO) drug administration of some anticancer agents can overcome drug resistance and increase drug efficacy in many cancers, but the mechanisms are not understood fully. Previously, we showed that METRO dosing of topotecan (TOPO) is more effective than conventional (CONV) dosing in aggressive human prostate cancer (PCa) cell lines and in mouse tumor xenograft models. To gain mechanistic insights into METRO-TOPO activity, in this study we determined the effect of METRO- and CONV-TOPO treatment in a panel of human PCa cell lines representing castration-sensitive/resistant, androgen receptor (+/−), and those of different ethnicity on cell growth and gene expression. Differentially expressed genes (DEGs) were identified for METRO-TOPO therapy and compared to a PCa patient cohort and The Cancer Genome Atlas (TCGA) database. The top five DEGs were SERPINB5, CDKN1A, TNF, FOS, and ANGPT1. Ingenuity Pathway Analysis predicted several upstream regulators and identified top molecular networks associated with METRO dosing, including tumor suppression, anti-proliferation, angiogenesis, invasion, metastasis, and inflammation. Further, the top DEGs were associated with increase survival of PCa patients (TCGA database), as well as ethnic differences in gene expression patterns in patients and cell lines representing African Americans (AA) and European Americans (EA). Thus, we have identified candidate pharmacogenomic biomarkers and novel pathways associated with METRO-TOPO therapy that will serve as a foundation for further investigation and validation of METRO-TOPO as a novel treatment option for prostate cancers.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shadi Eshghi Sahraei ◽  
Michelle Cleary ◽  
Jan Stenlid ◽  
Mikael Brandström Durling ◽  
Malin Elfstrand

Abstract Background With the expanding ash dieback epidemic that has spread across the European continent, an improved functional understanding of the disease development in afflicted hosts is needed. The study investigated whether differences in necrosis extension between common ash (Fraxinus excelsior) trees with different levels of susceptibility to the fungus Hymenoscyphus fraxineus are associated with, and can be explained by, the differences in gene expression patterns. We inoculated seemingly healthy branches of each of two resistant and susceptible ash genotypes with H. fraxineus grown in a common garden. Results Ten months after the inoculation, the length of necrosis on the resistant genotypes were shorter than on the susceptible genotypes. RNA sequencing of bark samples collected at the border of necrotic lesions and from healthy tissues distal to the lesion revealed relatively limited differences in gene expression patterns between susceptible and resistant genotypes. At the necrosis front, only 138 transcripts were differentially expressed between the genotype categories while 1082 were differentially expressed in distal, non-symptomatic tissues. Among these differentially expressed genes, several genes in the mevalonate (MVA) and iridoid pathways were found to be co-regulated, possibly indicating increased fluxes through these pathways in response to H. fraxineus. Comparison of transcriptional responses of symptomatic and non-symptomatic ash in a controlled greenhouse experiment revealed a relatively small set of genes that were differentially and concordantly expressed in both studies. This gene-set included the rate-limiting enzyme in the MVA pathway and a number of transcription factors. Furthermore, several of the concordantly expressed candidate genes show significant similarity to genes encoding players in the abscisic acid- or Jasmonate-signalling pathways. Conclusions A set of candidate genes, concordantly expressed between field and greenhouse experiments, was identified. The candidates are associated with hormone signalling and specialized metabolite biosynthesis pathways indicating the involvement of these pathways in the response of the host to infection by H. fraxineus.


2020 ◽  
Vol 60 (12) ◽  
pp. 1491
Author(s):  
Chinju Johnson ◽  
Carolyn Fitzsimmons ◽  
Igor Kovalchuk ◽  
John Kastelic ◽  
Jacob Thundathil

Context Selection for residual feed intake (RFI) and its impact on male reproductive development has had mixed reviews in the past. Our previous studies demonstrated earlier puberty, larger testes and greater percentage of progressively motile sperm in high-RFI bulls. However, the molecular mechanisms within testes of bulls with varying RFI remain unclear. Aims To determine the effect of RFI and pre-natal diet on the expression patterns of testicular genes and use this information to explain differences observed across RFI. Methods The study included 25 purebred-Angus bulls with a genetic background of either high or low RFI and fed either normal or low pre-natal nutrition from 30 to 150 days post conception. After slaughter (17 months), testicular tissue was recovered, and RNA was extracted and sequenced. Key results Of 19218 expressed genes, 17 were differentially expressed for RFI (including PLCD1, INPP4B), with no differences being observed for pre-natal diet or diet × RFI interaction (false discovery rate) < 0.1%). KEGG pathway analysis indicated that differentially expressed genes were associated with inositol phosphate metabolism, and phosphatidylinositol signalling. On the basis of a candidate gene-expression study, IGF1R was upregulated in high-RFI bulls (P < 0.1). Conclusions Increased expression of IGF1R and lowered PLCD1 and INPP4B expression could activate PI3K–Akt signalling responsible for cell growth, proliferation and steroid metabolism in high-RFI bulls. Implications Selecting bulls for feed efficiency might affect molecular networks associated with reproduction and fertility.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aliki Xanthopoulou ◽  
Javier Montero-Pau ◽  
Belén Picó ◽  
Panagiotis Boumpas ◽  
Eleni Tsaliki ◽  
...  

Abstract Background Summer squash (Cucurbita pepo: Cucurbitaceae) are a popular horticultural crop for which there is insufficient genomic and transcriptomic information. Gene expression atlases are crucial for the identification of genes expressed in different tissues at various plant developmental stages. Here, we present the first comprehensive gene expression atlas for a summer squash cultivar, including transcripts obtained from seeds, shoots, leaf stem, young and developed leaves, male and female flowers, fruits of seven developmental stages, as well as primary and lateral roots. Results In total, 27,868 genes and 2352 novel transcripts were annotated from these 16 tissues, with over 18,000 genes common to all tissue groups. Of these, 3812 were identified as housekeeping genes, half of which assigned to known gene ontologies. Flowers, seeds, and young fruits had the largest number of specific genes, whilst intermediate-age fruits the fewest. There also were genes that were differentially expressed in the various tissues, the male flower being the tissue with the most differentially expressed genes in pair-wise comparisons with the remaining tissues, and the leaf stem the least. The largest expression change during fruit development was early on, from female flower to fruit two days after pollination. A weighted correlation network analysis performed on the global gene expression dataset assigned 25,413 genes to 24 coexpression groups, and some of these groups exhibited strong tissue specificity. Conclusions These findings enrich our understanding about the transcriptomic events associated with summer squash development and ripening. This comprehensive gene expression atlas is expected not only to provide a global view of gene expression patterns in all major tissues in C. pepo but to also serve as a valuable resource for functional genomics and gene discovery in Cucurbitaceae.


2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2311
Author(s):  
Hao Ding ◽  
Yueyue Lin ◽  
Tao Zhang ◽  
Lan Chen ◽  
Genxi Zhang ◽  
...  

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.


Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 82
Author(s):  
Yunxiao Wei ◽  
Guoliang Li ◽  
Shujiang Zhang ◽  
Shifan Zhang ◽  
Hui Zhang ◽  
...  

Allopolyploidy is an evolutionary and mechanistically intriguing process involving the reconciliation of two or more sets of diverged genomes and regulatory interactions, resulting in new phenotypes. In this study, we explored the gene expression patterns of eight F2 synthetic Brassica napus using RNA sequencing. We found that B. napus allopolyploid formation was accompanied by extensive changes in gene expression. A comparison between F2 and the parent shows a certain proportion of differentially expressed genes (DEG) and activation\silent gene, and the two genomes (female parent (AA)\male parent (CC) genomes) showed significant differences in response to whole-genome duplication (WGD); non-additively expressed genes represented a small portion, while Gene Ontology (GO) enrichment analysis showed that it played an important role in responding to WGD. Besides, genome-wide expression level dominance (ELD) was biased toward the AA genome, and the parental expression pattern of most genes showed a high degree of conservation. Moreover, gene expression showed differences among eight individuals and was consistent with the results of a cluster analysis of traits. Furthermore, the differential expression of waxy synthetic pathways and flowering pathway genes could explain the performance of traits. Collectively, gene expression of the newly formed allopolyploid changed dramatically, and this was different among the selfing offspring, which could be a prominent cause of the trait separation. Our data provide novel insights into the relationship between the expression of differentially expressed genes and trait segregation and provide clues into the evolution of allopolyploids.


2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Michael A Burke ◽  
Stephen Chang ◽  
Danos C Christodoulou ◽  
Joshua M Gorham ◽  
Hiroko Wakimoto ◽  
...  

The complex molecular networks underpinning DCM remain poorly understood. To study distinct pathways and networks in the longitudinal development of DCM we performed RNAseq on LV tissue from mice carrying a human DCM mutation in phospholamban (PLN R9C/+ ) before phenotype onset (pre-DCM), with DCM, and during overt heart failure (HF), and also on isolated myocytes and non-myocytes from DCM hearts. PLN R9C/+ mice show progressive fibrosis (20% vs. 1% control, p=6x10 −33 ; n=3) associated with proliferation of cardiac non-myocytes (33% increase over control, p=6x10 −4 ; n=3). Consistent with this, cardiac non-myocytes have upregulated gene expression and pathways, while these are generally downregulated in myocytes. Non-myocytes were enriched in fibrosis, inflammation, and cell remodeling pathways, from pre-DCM to HF. In contrast, myocytes were enriched for metabolic pathways only with overt DCM and HF. Myocytes showed profound derangement of oxidative phosphorylation with DCM (p=2.5x10 −41 ; 44% (53/120) of pathway genes downregulated), suggesting mitochondrial dysfunction. Additionally, we detected probable inhibition of peroxisome proliferator-activated receptor (PPAR) signaling by diminished expression of pathway genes (Figure). DCM and hypertrophic remodeling was compared using RNAseq of a mouse model of HCM; similar patterns of fibrosis with myocyte metabolic dysregulation were evident despite unique differential gene expression patterns between models. DCM caused by PLN R9C/+ is associated with early non-myocyte proliferation and later myocyte metabolic derangement possibly governed by altered PPAR signaling, and is common to DCM and HCM.


2004 ◽  
Vol 17 (1) ◽  
pp. 11-20 ◽  
Author(s):  
David M. Mutch ◽  
Pascale Anderle ◽  
Muriel Fiaux ◽  
Robert Mansourian ◽  
Karine Vidal ◽  
...  

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.


2021 ◽  
Author(s):  
Graham L. Cromar ◽  
Jonathan Epp ◽  
Ana Popovic ◽  
Yusing Gu ◽  
Violet Ha ◽  
...  

ABSTRACTToxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.


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