Comparison of gene expression regulation in mouse- and human embryonic stem cell assays during neural differentiation and in response to valproic acid exposure
“…This can be explained based on the fact that mammals and poultry had different ancestors and they evolved differently. Instead, gene homology can be found for humans and a lack of mammals contributing to the use of same cell molecular marker in different species (Schulpen et al, 2015). The rodents, such as mice and rat, are important models for several human diseases because they have high gene homology and the results obtained in the rodent models can be extrapolated for humans (Huang et al, 2016).…”
ABSTRACT. Poultry production is faced with different types of stresses that are responsible for issues of animal welfare as well as for economic losses. Moreover, the immunity decreases when animals are stressed. In silico analyses are important in reducing the cost and in increasing the accuracy of scientific results. A bioinformatics tool was used to perform ontology studies on 15 different immunological sequences of poultry. The mRNA structures and sequences with maximum antigenic residues were also predicted. No homology was found between the sequences of poultry and mammals. These results helped in the prediction of new potential molecular markers. Of the 15 sequences that were analyzed, predictions could not be made for five because they were longer than 2500 nucleotides; for the remaining 10 sequences, 20 conformational 2 L.J. Lara et al.
Genetics and Molecular Research 16 (2): gmr16029423structures per sequence were predicted and the most stable sequences were identified by their minimum free energy values. The highest antigenic epitopes were accepted by the maximum scores; 15 of the total 8934 epitopes that were predicted were analyzed. These results would aid future studies that use synthetic peptides or recombinants as markers or immunomodulators and would expand our understanding on how stress can modulate the immune system. These would also help in developing rapid diagnostic tools, in increasing animal welfare, biosecurity, and productivity, and also in developing of food additives and environmental enrichment for stress control, thereby, making animal production more sustainable.
“…This can be explained based on the fact that mammals and poultry had different ancestors and they evolved differently. Instead, gene homology can be found for humans and a lack of mammals contributing to the use of same cell molecular marker in different species (Schulpen et al, 2015). The rodents, such as mice and rat, are important models for several human diseases because they have high gene homology and the results obtained in the rodent models can be extrapolated for humans (Huang et al, 2016).…”
ABSTRACT. Poultry production is faced with different types of stresses that are responsible for issues of animal welfare as well as for economic losses. Moreover, the immunity decreases when animals are stressed. In silico analyses are important in reducing the cost and in increasing the accuracy of scientific results. A bioinformatics tool was used to perform ontology studies on 15 different immunological sequences of poultry. The mRNA structures and sequences with maximum antigenic residues were also predicted. No homology was found between the sequences of poultry and mammals. These results helped in the prediction of new potential molecular markers. Of the 15 sequences that were analyzed, predictions could not be made for five because they were longer than 2500 nucleotides; for the remaining 10 sequences, 20 conformational 2 L.J. Lara et al.
Genetics and Molecular Research 16 (2): gmr16029423structures per sequence were predicted and the most stable sequences were identified by their minimum free energy values. The highest antigenic epitopes were accepted by the maximum scores; 15 of the total 8934 epitopes that were predicted were analyzed. These results would aid future studies that use synthetic peptides or recombinants as markers or immunomodulators and would expand our understanding on how stress can modulate the immune system. These would also help in developing rapid diagnostic tools, in increasing animal welfare, biosecurity, and productivity, and also in developing of food additives and environmental enrichment for stress control, thereby, making animal production more sustainable.
“…However, the EST uses mouse cells, and species-specific differences must be clarified in order to use this approach to evaluate toxicity in human. Subsequently, another research group reported that in an EST based on a human cell system (hEST), changes in the expression of homologous neurodevelopmental genes were similar to those observed in the mouse system 5 .…”
SUMMARYThe assessment of toxic chemicals using animals has limited applicability to humans. Moreover, from the perspective of animal protection, effective alternatives are also desired. Previously, we developed a method that combines developmental toxicity testing based on undifferentiated human embryonic stem (ES) cells (KhES-3) and gene networks. We showed that ≥ 95% accurate predictions could be achieved for neurotoxins, genotoxic carcinogens, and non-genotoxic carcinogens. Here, we expanded this method to predict broad toxicities and predicted the toxicity of 24 chemicals in six categories (neurotoxins, cardiotoxins, hepatotoxins, nephrotoxins [glomerular nephrotoxins/tubular nephrotoxins], and non-genotoxic carcinogens) and achieved high prediction accuracy (AUC = 0.90–1.00) in all categories. Moreover, to develop a testing system with fewer ethical issues, we screened for an induced pluripotent stem (iPS) cell line on the basis of cytotoxic sensitivity and used this line to predict toxicity in the six categories based on the gene networks of iPS cells using transfer learning from the ES cell gene networks. We successfully predicted toxicities in four toxin categories (neurotoxins, hepatotoxins, glomerular nephrotoxins, and non-genotoxic carcinogens) at high accuracy (AUC = 0.82–0.99). These results demonstrate that the prediction of chemical toxicity is possible even with iPS cells by transfer learning once a gene expression database has been developed from an ES cell line. This method holds promise for tailor-made safety evaluations using individual iPS cells.
“…However, the EST uses mouse cells, and species-specific differences must be clarified in order to extrapolate its results to human. Subsequently, another research group reported that in an EST based on a human cell system (hEST), homologous human and mouse neurodevelopmental gene expressions are similar ( Schulpen et al., 2015 ). Moreover, there is an extensive collection of literature on the research and development of pluripotent stem cell models for predictive toxicology, including assays based on specific biomarkers such as Hand-1 and Sox17 ( Kameoka et al., 2014 ; Suzuki et al., 2011 ), assays customized to specific toxicities such as teratogenicity ( West et al., 2010 ), models for relevant pathways such as Wnt signaling or TGF-b ( Kugler et al., 2015 ; Uibel et al., 2010 ), detected by various modalities such as luciferase reporter, metabolomics, high-throughput imaging ( Kameoka et al., 2014 ; Kleinstreuer et al., 2011 ; Uibel et al., 2010 ), and others, which have been summarized in the review papers of Luz and Tokar (2018) and Kim et al.…”
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