Decabromodiphenyl ethane (DBDPE) inhibited the growth and feeding by disrupting the gut and digestive gland homeostasis in octopus Amphioctopus fangsiao (Mollusca: Cephalopoda).

A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) poses a potential threat to animals, but its effects on cephalopods remain unknown. In this study, Amphioctopus fangsiao, a common octopus in China, was exposed to DBDPE (0, 1, 50, 100, 300 µg/L) for 28 days. Chemical analysis revealed that the digestive gland bore a greater burden of DBDPE compared with other tissues. In addition, accumulated DBDPE could curb the growth and feeding performance of A. fangsiao. The potential effects on the "gut-digestive gland axis" were also elucidated. Specifically, DBDPE in the gut shifted the microorganisms toward a Bacteroidetes-dominated composition, and impaired the intestinal epithelial barrier, thereby triggering oxidative stress and inflammation. Excessive DBDPE also threatens the digestive gland function, including histological damage, immune reaction, oxidative stress, glucolipid metabolism dysfunction, and neurotoxicity. Metabolome plasticity enabled A. fangsiao to develop a DBDPE stress-adaptive metabolic profile via alteration of glucolipid metabolism, immunity, oxidative stress, and signaling molecules. Taken together, we identified a new detoxification mechanism linking the microbiota-gut-digestive gland axis with the growth and food intake of A. fangsiao, which is the first time it has been demonstrated in mollusks. These findings provided important clues for a further mechanism study and risk assessment of DBDPE.

Effects of rumen metabolite butyric acid on bovine skeletal muscle satellite cells proliferation, apoptosis and transcriptional states during myogenic differentiation.

Butyric acid, a pivotal short-chain fatty acid in rumen digestion, profoundly influences animal digestive and locomotor systems. Extensive research indicates its direct or indirect involvement in the growth and development of muscle and fat cells. However, the impact of butyric acid on the proliferation and differentiation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. This study aimed to elucidate the effects of butyrate on SMSCs proliferation and differentiation. After isolating, SMSCs were subjected to varying concentrations of sodium butyrate (NaB) during the proliferation and differentiation stages. Optimal treatment conditions (1 mM NaB for 2 days) were determined based on proliferative force, cell viability, and mRNA expression of proliferation and differentiation marker genes. Transcriptome sequencing was employed to screen for differential gene expression between 1 mM NaB-treated and untreated groups during SMSCs differentiation. Results indicated that lower NaB concentrations (≤1.0 mM) inhibited proliferation while promoting differentiation and apoptosis after a 2-day treatment. Conversely, higher NaB concentrations (≥2.0 mM) suppressed proliferation and differentiation and induced apoptosis. Transcriptome sequencing revealed differential expression of genes(ND1, ND3, CYTB, COX2, ATP6, MYOZ2, MYOZ3, MYBPC1 and ATP6V0A4,etc.) were associated with SMSCs differentiation and energy metabolism, enriching pathways such as Oxidative phosphorylation, MAPK, and Wnt signaling. These findings offer valuable insights into the molecular mechanisms underlying butyrate regulation of bovine SMSCs proliferation and differentiation, as well as muscle fiber type conversion in the future study.

Transcriptomic profiling of gastrointestinal tracts in dairy cattle during lactation reveals molecular adaptations for milk synthesis.

During lactation, dairy cattle's digestive tract requires significant adaptations to meet the increased nutrient demands for milk production. As we attempt to improve milk-related traits through selective pressure, it is crucial to understand the biological functions of the epithelia of the rumen, small intestine, and colonic tissues in response to changes in physiological state driven by changes in nutrient demands for milk synthesis. In this study, we obtained a total of 108 transcriptome profiles from three tissues (epithelia of the colon, duodenum, and rumen) of five Holstein cows, spanning eight time points from the early, mid, late lactation periods to the dry period. On average 97.06% of reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We analyzed 27,607 gene expression patterns at multiple periods, enabling direct comparisons within and among tissues during different lactation stages, including early and peak lactation. We identified 1645, 813, and 2187 stage-specific genes in the colon, duodenum, and rumen, respectively, which were enriched for common or specific biological functions among different tissues. Time series analysis categorized the expressed genes within each tissue into four clusters. Furthermore, when the three tissues were analyzed collectively, 36 clusters of similarly expressed genes were identified. By integrating other comprehensive approaches such as gene co-expression analyses, functional enrichment, and cell type deconvolution, we gained profound insights into cattle lactation, revealing tissue-specific characteristics of the gastrointestinal tract and shedding light on the intricate molecular adaptations involved in nutrient absorption, immune regulation, and cellular processes for milk synthesis during lactation.

CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Unraveling the Genetic Basis of Feed Efficiency in Cattle through Integrated DNA Methylation and CattleGTEx Analysis.

Feed costs can amount to 75 percent of the total overhead cost of raising cows for milk production. Meanwhile, the livestock industry is considered a significant contributor to global climate change due to the production of greenhouse gas emissions, such as methane. Indeed, the genetic basis of feed efficiency (FE) is of great interest to the animal research community. Here, we explore the epigenetic basis of FE to provide base knowledge for the development of genomic tools to improve FE in cattle. The methylation level of 37,554 CpG sites was quantified using a mammalian methylation array (HorvathMammalMethylChip40) for 48 Holstein cows with extreme residual feed intake (RFI). We identified 421 CpG sites related to 287 genes that were associated with RFI, several of which were previously associated with feeding or digestion issues. Activator of transcription and developmental regulation (AUTS2) is associated with digestive disorders in humans, while glycerol-3-phosphate dehydrogenase 2 (GPD2) encodes a protein on the inner mitochondrial membrane, which can regulate glucose utilization and fatty acid and triglyceride synthesis. The extensive expression and co-expression of these genes across diverse tissues indicate the complex regulation of FE in cattle. Our study provides insight into the epigenetic basis of RFI and gene targets to improve FE in dairy cattle.

Sodium Butyrate Induces Mitophagy and Apoptosis of Bovine Skeletal Muscle Satellite Cells through the Mammalian Target of Rapamycin Signaling Pathway.

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. Skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited proliferation, promoted apoptosis of BSCs, and promoted mitophagy in a time- and dose-dependent manner in BSCs. In addition, 1 mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA (mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated. The results showed that 1 mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway. In contrast, the addition of PP242, an inhibitor of the mTOR signaling pathway also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1 and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.

The single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells in Chinese holstein cattle.

OBJECTIVES: This study was performed in the frame of a more extensive study dedicated to the integrated analysis of the single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells (PBMCs) with a large-scale GWAS of 45 complex traits in Chinese Holstein cattle. Lipopolysaccharide (LPS) is a crucial mediator of chronic inflammation to modulate immune responses. PBMCs include primary T and B cells, natural killer (NK) cells, monocytes (Mono), and dendritic cells (DC). How LPS stimulates PBMCs at the single-cell level in dairy cattle remains largely unknown. DATA DESCRIPTION: We sequenced 30,756 estimated single cells and mapped 26,141 of them (96.05%) with approximately 60,075 mapped reads per cell after quality control for four whole-blood treatments (no, 2 h, 4 h, and 8 h LPS) by single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq). Finally, 7,107 (no), 9,174 (2 h), 6,741 (4 h), and 3,119 (8 h) cells were generated with ~ 15,000 total genes in the whole population. Therefore, the single-cell transcriptome and chromatin accessibility datasets in this study enable a further understanding of the cell types and functions of PBMCs and their responses to LPS stimulation in vitro.

Codon Usage Bias Analysis in Macronuclear Genomes of Ciliated Protozoa.

Ciliated protozoa (ciliates) are unicellular eukaryotes, several of which are important model organisms for molecular biology research. Analyses of codon usage bias (CUB) of the macronuclear (MAC) genome of ciliates can promote a better understanding of the genetic mode and evolutionary history of these organisms and help optimize codons to improve gene editing efficiency in model ciliates. In this study, the following indices were calculated: the guanine-cytosine (GC) content, the frequency of the nucleotides at the third position of codons (T3, C3, A3, G3), the effective number of codons (ENc), GC content at the 3rd position of synonymous codons (GC3s), and the relative synonymous codon usage (RSCU). Parity rule 2 plot analysis, Neutrality plot analysis, ENc plot analysis, and correlation analysis were employed to explore the main influencing factors of CUB. The results showed that the GC content in the MAC genomes of each of 21 ciliate species, the genomes of which were relatively complete, was lower than 50%, and the base compositions of GC and GC3s were markedly distinct. Synonymous codon analysis revealed that the codons in most of the 21 ciliates ended with A or T and four codons were the general putative optimal codons. Collectively, our results indicated that most of the ciliates investigated preferred using the codons with anof AT-ending and that codon usage bias was affected by gene mutation and natural selection.

Genome-Wide Acetylation Modification of H3K27ac in Bovine Rumen Cell Following Butyrate Exposure.

Butyrate contributes epigenetically to the changes in cellular function and tissue development of the rumen in ruminant animals, which might be achieved by its genetic or epigenetic regulation of gene expression. To explore the role of butyrate on bovine rumen epithelial function and development, this study characterized genome-wide H3K27ac modification changes and super-enhancer profiles in rumen epithelial primary cells (REPC) induced with butyrate by ChIP-seq, and analyzed its effects on gene expression and functional pathways by integrating RNA-seq data. The results showed that genome-wide acetylation modification was observed in the REPC with 94,675 and 48,688 peaks in the butyrate treatment and control group, respectively. A total of 9750 and 5020 genes with increased modification (H3K27ac-gain) and decreased modification (H3K27ac-loss) were detected in the treatment group. The super-enhancer associated genes in the butyrate-induction group were involved in the AMPK signaling pathway, MAPK signaling pathway, and ECM-receptor interaction. Finally, the up-regulated genes (PLCG1, CLEC3B, IGSF23, OTOP3, ADTRP) with H3K27ac gain modification by butyrate were involved in cholesterol metabolism, lysosome, cell adhesion molecules, and the PI3K-Akt signaling pathway. Butyrate treatment has the role of genome-wide H3K27ac acetylation on bovine REPC, and affects the changes in gene expression. The effect of butyrate on gene expression correlates with the acetylation of the H3K27ac level. Identifying genome-wide acetylation modifications and expressed genes of butyrate in bovine REPC cells will expand the understanding of the biological role of butyrate and its acetylation.

Comparative transcriptome and antioxidant biomarker response reveal molecular mechanisms to cope with zinc ion exposure in the unicellular eukaryote Paramecium.

The development of industry has resulted in excessive environmental zinc exposure which has caused various health problems in a wide range of organisms including humans. The mechanisms by which aquatic microorganisms respond to environmental zinc stress are still poorly understood. Paramecium, a well-known ciliated protozoan and a popular cell model in heavy metal stress response studies, was chosen as the test unicellular eukaryotic organism in the present research. In this work, Paramecium cf. multimicronucleatum cells were exposed in different levels of zinc ion (0.1 and 1.0 mg/L) for different periods of exposure (1 and 4 days), and then analyzed population growth, transcriptomic profiles and physiological changes in antioxidant enzymes to explore the toxicity and detoxification mechanisms during the zinc stress response. Results demonstrated that long-term zinc exposure could have restrained population growth in ciliates, however, the response mechanism to zinc exposure in ciliates is likely to show a dosage-dependent and time-dependent manner. The differentially expressed genes (DEGs) were identified the characters by high-throughput sequencing, which remarkably enriched in the phagosome, indicating that the phagosome pathway might mediate the uptake of zinc, while the pathways of ABC transporters and Na+/K+-transporting ATPase contributed to the efflux transport of excessive zinc ions and the maintenance of osmotic balance, respectively. The accumulation of zinc ions triggered a series of adverse effects, including damage to DNA and proteins, disturbance of mitochondrial function, and oxidative stress. In addition, we found that gene expression changed significantly for metal ion binding, energy metabolism, and oxidation-reduction processes. RT-qPCR of ten genes involved in important biological functions further validated the results of the transcriptome analysis. We also continuously monitored changes in activity of four antioxidant enzymes (SOD, CAT, POD and GSH-PX), all of which peaked on day 4 in cells subjected to zinc stress. Collectively, our results indicate that excessive environmental zinc exposure initially causes damage to cellular structure and function and then initiates detoxification mechanisms to maintain homeostasis in P. cf. multimicronucleatum cells.

Atorvastatin reduces contrast media-induced pyroptosis of renal tubular epithelial cells by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI. METHODS: On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells. RESULTS: MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65). CONCLUSION: Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.

Dietary intake of microplastics impairs digestive performance, induces hepatic dysfunction, and shortens lifespan in the annual fish Nothobranchius guentheri.

Microplastics (MPs) are ubiquitous in aquatic and terrestrial ecosystem, increasingly becoming a serious concern of human health. Many studies have explored the biological effects of MPs on animal and plant life in recent years. However, information regarding the effects of MPs on aging and lifespan is completely lacking in vertebrate species to date. Here we first confirm the bioavailability of MPs by oral delivery in the annual fish N. guentheri. We then show for the first time that administration of MPs not only shortens the lifespan but also accelerates the development of age-related biomarkers in N. guentheri. We also demonstrate that administration of MPs induces oxidative stress, suppresses antioxidant enzymes, reduces digestive enzymes, and causes hepatic dysfunction. Therefore, we propose that administration of MPs reduces lifespan of N. guentheri via induction of both suppressed antioxidant system and digestive disturbance as well as hepatic damage. Our results also suggest that smaller MPs appear more toxic to digestion, metabolism and growth of animals.

Polystyrene microplastic ingestion induces the damage in digestive gland of Amphioctopus fangsiao at the physiological, inflammatory, metabolome and transcriptomic levels.

Microplastics are ubiquitous in the aquatic and terrestrial ecosystem, increasingly becoming a serious concern for aquatic organism health. However, information regarding the effects of microplastics on cephalopods is remain limited to date. Amphioctopus fangsiao, an important economic species in cephalopods, can serve as a potential indicator of environmental pollution due to its short life expectancy and high metabolic rates. Here, to explore the toxic effects during the microplastic stress response, we analyzed the growth performance, histopathological damage, oxidative stress biomarkers, metabolomic and transcriptomic response in digestive gland of A. fangsiao under different concentrations (0, 100 and 1000 µg/L) of commercial polystyrene microplastics (MPS) exposure (5 µm, sphere) for 21 days. The results showed that MPS exerted a huge influence on the growth performance of A. fangsiao. The oxidative stress and inflammation in digestive gland of A. fangsiao were also detected after exposure to MPS. In addition, most of the altered metabolites observed in the metabolic analysis were related to inflammation, oxidative stress and glucolipid metabolism. Transcriptome analysis detected the differentially expressed genes (DEGs) and the significantly enriched KEGG pathways associated with glycolipid metabolism, inflammation and DNA damage. Collectively, our results indicate that excessive environmental microplastic exposure will cause toxicity damage and then initiate the detoxification mechanism in A. fangsiao digestive gland to maintain homeostasis. This study revealed that microplastic can cause adverse consequences on cephalopods, providing novel insights into the toxicological effect of microplastic exposure.

Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells.

Butyrate is produced in the rumen from microbial fermentation and is related to several functions, including cell differentiation and proliferation. Butyrate supplementation in calves can accelerate rumen development. DNA-protein interactions, such as the CCCTC-binding factor (CTCF), play essential roles in chromatin organization and gene expression regulation. Although CTCF-binding sites have been identified recently in cattle, a deeper characterization, including differentially CTCF-binding sites (DCBS), is vital for a better understanding of butyrate's role in the chromatin landscape. This study aimed to identify CTCF-binding regions and DCBS under a butyrate-induced condition using ChIP-seq in bovine cells; 61,915 CTCF peaks were identified in the butyrate and 51,347 in the control. From these regions, 2265 DCBS were obtained for the butyrate vs. control comparison, comprising ~90% of induced sites. Most of the butyrate DCBS were in distal intergenic regions, showing a potential role as insulators. Gene ontology enrichment showed crucial terms for the induced DCBS, mainly related to cellular proliferation, cell adhesion, and growth regulation. Interestingly, the ECM-receptor interaction pathway was observed for the induced DCBS. Motif enrichment analysis further identified transcription factors, including CTCF, BORIS, TGIF2, and ZIC3. When DCBS was integrated with RNA-seq data, putative genes were identified for the repressed DCBS, including GATA4. Our study revealed promising candidate genes in bovine cells by a butyrate-induced condition that might be related to the regulation of rumen development, such as integrins, keratins, and collagens. These results provide a better understanding of the function of butyrate in cattle rumen development and chromatin landscape regulation.

Toxic effects of polystyrene microplastics on the intestine of Amphioctopus fangsiao (Mollusca: Cephalopoda): From physiological responses to underlying molecular mechanisms.

Microplastics are broadly used and among the most studied environmental pollutants due to their potential impacts on organisms and human health. Amphioctopus fangsiao (Cephalopoda: Octopodidae) is an important commercial species in the Pacific Northwest and is very popular among consumers owing to its rich nutritional value and fresh flavor. However, the toxic effects of microplastic exposure on A. fangsiao, including phenotypical effect and underlying molecular mechanism, remain limited. In this study, the octopus A. fangsiao were exposed to microplastics (polystyrene microplastics, Micro-PS) at concentrations of 100 and 1000 µg/L for 21 days, and then the physiological response, histopathological analysis, biomarkers of oxidative stress and glycolipid metabolism, microbiome perturbations and transcriptomic profiles in the intestines were performed. Results demonstrated that Micro-PS exposure had distinct adverse effects on the food intake of A. fangsiao. Histological analysis revealed that Micro-PS exposure has resulted in histopathological damage, thus causing early inflammation of the intestine. Oxidative stresses, metabolic disorders and microbiome perturbations were also detected in the intestine of A. fangsiao based on physiological biomarkers and microbiome analyses. Moreover, transcriptome analysis detected the differentially expressed genes (DEGs) and significantly enriched KEGG pathways in response to oxidative stress, glycolipid metabolism, DNA damage and transmembrane transport of intestinal cells, revealing distinct toxic effects at the molecular level. In summary, Micro-PS exposure has a strong impact on the intestines of A. fangsiao. For the first time, this study uses multiple approaches based on the physiological and biochemical response as well as transcriptional regulation analysis. The first assessment of the toxic impact of this species under Micro-PS exposure is also reported.

Comparative transcriptome in large-scale human and cattle populations.

BACKGROUND: Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes. RESULTS: Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues. CONCLUSIONS: In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.

A multi-tissue atlas of regulatory variants in cattle.

Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype-Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.

Differentially CTCF-Binding Sites in Cattle Rumen Tissue during Weaning.

The weaning transition in calves is characterized by major structural changes such as an increase in the rumen capacity and surface area due to diet changes. Studies evaluating rumen development in calves are vital to identify genetic mechanisms affected by weaning. This study aimed to provide a genome-wide characterization of CTCF-binding sites and differentially CTCF-binding sites (DCBS) in rumen tissue during the weaning transition of four Holstein calves to uncover regulatory elements in rumen epithelial tissue using ChIP-seq. Our study generated 67,280 CTCF peaks for the before weaning (BW) and 39,891 for after weaning (AW). Then, 7401 DCBS were identified for the AW vs. BW comparison representing 0.15% of the cattle genome, comprising ~54% of induced DCBS and ~46% of repressed DCBS. Most of the induced and repressed DCBS were in distal intergenic regions, showing a potential role as insulators. Gene ontology enrichment revealed many shared GO terms for the induced and the repressed DCBS, mainly related to cellular migration, proliferation, growth, differentiation, cellular adhesion, digestive tract morphogenesis, and response to TGFß. In addition, shared KEGG pathways were obtained for adherens junction and focal adhesion. Interestingly, other relevant KEGG pathways were observed for the induced DCBS like gastric acid secretion, salivary secretion, bacterial invasion of epithelial cells, apelin signaling, and mucin-type O-glycan biosynthesis. IPA analysis further revealed pathways with potential roles in rumen development during weaning, including TGFß, Integrin-linked kinase, and Integrin signaling. When DCBS were further integrated with RNA-seq data, 36 putative target genes were identified for the repressed DCBS, including KRT84, COL9A2, MATN3, TSPAN1, and AJM1. This study successfully identified DCBS in cattle rumen tissue after weaning on a genome-wide scale and revealed several candidate target genes that may have a role in rumen development, such as TGFß, integrins, keratins, and SMADs. The information generated in this preliminary study provides new insights into bovine genome regulation and chromatin landscape.

Investigation of rumen long noncoding RNA before and after weaning in cattle.

BACKGROUND: This study aimed to identify long non-coding RNA (lncRNA) from the rumen tissue in dairy cattle, explore their features including expression and conservation levels, and reveal potential links between lncRNA and complex traits that may indicate important functional impacts of rumen lncRNA during the transition to the weaning period. RESULTS: A total of six cattle rumen samples were taken with three replicates from before and after weaning periods, respectively. Total RNAs were extracted and sequenced with lncRNA discovered based on size, coding potential, sequence homology, and known protein domains. As a result, 404 and 234 rumen lncRNAs were identified before and after weaning, respectively. However, only nine of them were shared under two conditions, with 395 lncRNAs found only in pre-weaning tissues and 225 only in post-weaning samples. Interestingly, none of the nine common lncRNAs were differentially expressed between the two weaning conditions. LncRNA averaged shorter length, lower expression, and lower conservation scores than the genome overall, which is consistent with general lncRNA characteristics. By integrating rumen lncRNA before and after weaning with large-scale GWAS results in cattle, we reported significant enrichment of both pre- and after-weaning lncRNA with traits of economic importance including production, reproduction, health, and body conformation phenotypes. CONCLUSIONS: The majority of rumen lncRNAs are uniquely expressed in one of the two weaning conditions, indicating a functional role of lncRNA in rumen development and transition of weaning. Notably, both pre- and post-weaning lncRNA showed significant enrichment with a variety of complex traits in dairy cattle, suggesting the importance of rumen lncRNA for cattle performance in the adult stage. These relationships should be further investigated to better understand the specific roles lncRNAs are playing in rumen development and cow performance.