卷 10, 编号 2 (2016)

In this study, we compared the ability of human mesenchymal stem cells (eMSCs) derived from menstrual blood and mesenchymal stem cells (MSCs) from other tissues to differentiate into decidual cells in vitro. It was demonstrated that, during differentiation, secretion of prolactin and insulin-like growth factor binding protein-1 (key decidualization markers) markedly increased in eMSCs slightly augmented in bone marrow MSC (BM-MSCs) and did not change in MSCs from adipose tissue (AT-MSCs). Thus, eMSCs exhibited higher capacity for differentiation into decidual cells than BM-MSCs or AT-MSCs. This makes eMSCs promising for application in cellular therapy of infertility associated with insufficient decidualization of endometrium.

Plakophilin-2 is a desmosomal protein encoded by PKP2 gene. Desmosomal proteins are usually considered as structural proteins with the main function of maintaining intercellular interactions. Genetic studies revealed that mutations in desmosomal genes could lead to arrhythmogenic right ventricular cardiomyopathy, a heart disease characterized by substitution of cardiomyocytes by adipose and fibrotic tissue predominantly in the right ventricle. Wnt signaling is a signal transduction pathway presumably involved in the development of pathology. The purpose of this study was to investigate Wnt activity in cells with wild-type and mutant PKP2 gene during adipogenic and cardiomyogenic differentiation. We used multipotent mesenchymal stromal cells and iPS cells generated from a patient carrying PKP2 gene mutation. We found that cells with mutant PKP2 exhibited lower transcriptional activity of β-catenin, a key player of Wnt signaling, as well as attenuated expression of its targets SOX2 and SOX9. These findings suggest a signaling role of plakophilin2 by regulating Wnt activity

Design and development of highly sensitive methods of bioinformatics are aßsociated with the need to obtain information on the impact of epigenetic changes on gene activity. One factor causing such changes is polyploidy. Polyploidy maintains the balance of gene dosage and, therefore, can have only a slight effect on their expression. Currently, there is no unified concept with respect to the impact of polyploidy on transcriptomes. To clarify this issue, we developed an integrative bioinformatics method aimed at accessing weak effects of polyploidy on the activity of genes by implementing a pairwise cross-transcriptome analysis of mammalian tissues with varying degrees of ploidy. The advantage of this method is its ability to distinguish between variable speciesand tissue-specific effects and evolutionarily conserved ones. The applicability of the developed methodology was demonstrated by analysis of genetic modules and protein interaction networks involved in the coordination of developmental processes. We carried out analysis of full transcriptome data for human and mouse heart and liver. We discovered that genes activated by ploidy are enriched (i.e., are presented above the random level) in transcriptomes of biological processes of the Gene Ontology (GO) database and in pathways in the KEGG database related to organism development, morphogenesis, and stem cell biology (including the signaling pathways Hippo, Pi3K, WNT, Hedgehog, and TGF-ß) to a greater extent than genes suppressed by ploidy. The structure and composition of the protein interaction networks constructed for ploidy regulated genes confirmed the results of analysis of gene modules. Thus, our data are the first to demonstrate that polyploidy can regulate the modules of organism development by increasing their activity.

Human umbilical vein endothelial cells were exposed in culture to hydrogen peroxide (H₂O₂), keeping them close to physiological conditions (high cell density, high serum content, H₂O₂ concentration not over 500 µM). Cell viability was assessed by flow cytometry using simultaneous staining with the fluorescent dye PO-PRO-1 to detect early apoptotic cells and DRAQ7 to detect late apoptotic and necrotic cells. The data obtained suggest that the primary mechanism of the cytotoxic response to H₂O₂ is apoptosis. The critical concentration of H₂O₂ causing death in a dense monolayer is 250 µM. Lower H₂O₂ concentrations (up to 200 µM) cause death of individual cells. The population of endothelial cell retains viability and response to calcium activating agonists does not change compared to control cells.

Salinity is one of the most important abiotic environmental factors for marine animals. If salinity deviates from optimum, adaptive mechanisms switch on to maintain organism’s physiological activity. In this study the proteome of the marine snails Littorina saxatilis from natural habitats (12, 23 and 32‰ and in response to experimental salinity decreasing (from 20‰ to 10‰) was analyzed. The isolation of all snails inside their shells and gradually declining mortality was observed under an acute experimental salinity decrease. Proteomic changes were evaluated in the survived experimental mollusks compared to control individuals using differential 2D gel-electrophoresis (DIGE) and subsequent LC-MS/MS-identification of proteins. Approximately 10% of analyzed proteins underwent upor down regulation during the experiment. Proteins of folding, antioxidant response, intercellular matrix, and metabolic enzymes were identified among them. Proteomic changes observed in experimental hypoosmotic stress partially reproduced in the proteomes of molluscs that live in conditions of natural freshening (estuaries). Possible mechanisms involved in the adaptation process of L. saxatilis individuals to hypoosmotic stress are discussed.