Genes & Cells最新文献

{"title":"Design of iPSC-based cell model to study the functions of the UBE2A gene","authors":"A. Bogomazova, A. V. Fedorenko, Ekaterina A. Khomyakova, Anastasia V. Surdina, E. K. Sekretova, Tatiana V. Limanskaya, L. D. Belikova, Egor A. Volovikov, M. Gridina, A. Khabarova, A. Kashevarova, Dmitry A. Fedotov, E. Zerkalenkova, M. A. Lagarkova, Igor N Lebedev","doi":"10.17816/gc623799","DOIUrl":"https://doi.org/10.17816/gc623799","url":null,"abstract":"BACKGROUND: The UBE2A protein belongs to the E2 family of ubiquitin-binding enzymes involved in the ubiquitination of substrate proteins. Mutations in the UBE2A gene lead to congenital X-linked mental retardation syndrome type Nascimento. It is still unknown how UBE2A participates in the development of the central nervous system. \u0000AIM: We aimed to establish a cell model based on induced pluripotent stem cells (iPSCs) to study the molecular and cellular functions of the UBE2A gene in neurogenesis. \u0000METHODS: Using genomic CRISPR-Cas9 editing and lentiviral transduction, we designed a cell model based on IPSCs from two healthy donors. This cell model includes isogenic iPSCs with knockout and inducible hyperexpression of the UBE2A gene. In addition, we obtained iPSCs by reprogramming peripheral blood mononuclear cells of a patient diagnosed with X-linked mental retardation of Nascimento type, which has a deletion spanning the whole UBE2A gene locus. \u0000RESULTS: The obtained iPSCs demonstrate ESC-like morphology. They express pluripotent cell markers OCT4, SOX2, SSEA-4, and TRA1-81 and have normal karyotypes. We found that IPSCs with UBE2A gene knockout or hyperexpression had significantly increased nuclei size compared to isogenic control. \u0000CONCLUSION: We established the iPSC-based cell model, which can be used for fundamental studies of the UBE2A gene functions in neurogenesis.","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141384987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of storage conditions on the viability of spheroids from human chondrocytes","authors":"P. Golubinskaya, Arina S. Pikina, E. S. Ruchko, Artyom V. Eremeev","doi":"10.17816/gc623960","DOIUrl":"https://doi.org/10.17816/gc623960","url":null,"abstract":"","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"40 s4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141383278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PROTEOMIC AND TRANSCRIPTOMIC RESPONSE OF HUMAN SKELETAL MUSCLE TO 12-WEEK RESISTANCE TRAINING","authors":"E. M. Lednev, T. F. Vepkhvadze, Igor P. Smirnov, Rinat I. Sultanov, Andrey V. Zhelankin, Alexandra V. Kanygina, D. Popov, E. Generozov","doi":"10.17816/gc624325","DOIUrl":"https://doi.org/10.17816/gc624325","url":null,"abstract":"","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"45 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141383042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exome-wide association study for replication of rare variants affecting the severity of COVID-19 in the Russian population","authors":"S. Apalko, A. Nostaeva, V. Shimansky, N. Sushentseva, O. Popov, A. Anisenkova, S. Mosenko, O. Glotov, A. Sarana, S. Scherbak","doi":"10.17816/gc624810","DOIUrl":"https://doi.org/10.17816/gc624810","url":null,"abstract":"BACKGROUND: Human genetics is one of the factors determining the severity of COVID-19 disease. Previously, a large-scale whole-genome association study of the COVID-19 HG project (COVID-19 Host Genetics Initiative, 2021) investigated the association of genetic variants at multiple loci with COVID-19 severity. The genetic variants that have the greatest impact on COVID-19 severity are expected to have a low frequency in the population. Therefore, the study of rare variants may provide additional insights into the pathogenesis of the disease and thus help in the development of prevention and treatment options. \u0000AIM: The aim is to perform a replication analysis in search of genes with enrichment for rare genetic variants in relation to the severity of COVID-19 disease. \u0000METHODS: In this study, the clinical exome of a Russian cohort of patients was sequenced based on the St. Petersburg State Budgetary Institution \"City Hospital No. 40\" and St. Petersburg State University. The study used biomaterial from patients hospitalised at \"City Hospital No. 40\" with a diagnosis of COVID-19 and healthy individuals included in the population control group. The severity of the course of COVID-19 was determined according to the results of lung computed tomography. The list of genes for subsequent replication was generated by a literature review. Replication analysis of genes associated with COVID-19 severity was performed using burden test methods. \u0000RESULTS: In total, 701 clinical exomes were sequenced: 263 severe COVID-19 and 438 healthy individuals. A literature review identified 18 genes associated with severe COVID-19 that were included in the replication analysis. The replication analysis did not identify any genes whose association with severe COVID-19 was confirmed in the study cohort. \u0000CONCLUSION: Replication analysis did not identify any genes for which a significant association between functional variant enrichment and COVID-19 severity was found. However, the results demonstrated that the direction of the correlation was consistent with findings from previous studies. The small size of the sample analysed is an obvious limitation of our study. Expanding the study cohort would increase the power of the tests and allow us to detect additional rare variants that influence the severity of COVID-19 progression","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"22 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAIN NEUROTROPHIC FACTOR BDNF: NEW DATA, FUNCTIONS AND QUESTIONS","authors":"Maryana Zhivkovich, Elizaveta Ermolaeva, Alesya Soboleva, Ekaterina Samoilova, Daria Chudakova, Vladimir Baklaushev","doi":"10.17816/gc623163","DOIUrl":"https://doi.org/10.17816/gc623163","url":null,"abstract":"Brain-derived neurotrophic factor BDNF is one of the key modulators of neurogenesis, synaptogenesis, neuroregeneration and cell differentiation in the nervous system (NS). Impaired functioning of BDNF is a characteristic of many neurological diseases, such as Alzheimer's disease, multiple sclerosis, depressive disorders and others. There is also recent evidence that patients with COVID-19 have reduced BDNF levels in the blood plasma.At the same time, exogenous BDNF or its mimetics have demonstrated therapeutic potential. In this review, we systematized data on the structure of theBDNFgene, epigenetic and microRNA-mediated regulation of its expression, transcriptional variants ofBDNF,and effect of BDNF on neuronal and oligodendroglial differentiation.We also point out the gaps in the current knowledge about BDNF,and propose experiments that can expand such knowledge and, subsequently, the range of possibilities for using BDNF in biomedicine.These include determining the expression pattern of allBDNFgene transcripts at different stages of differentiation and in different cell subpopulations, studying the role of receptor-independent BDNF signaling, circadian fluctuations in BDNF levels and their role in physiological and pathophysiological conditions.Finally, for translational medicine, it is of practical interest to assess the effect of BDNF mimetics (including those immobilized on three-dimensional scaffolds for tissue engineering) on neuronal and oligodendroglial differentiation of pluripotent and polypotent cells, as well as to identify molecular regulators ofBDNFtranscription including small molecules and microRNAs capable of regulatingBDNFgene expression.","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"206 1‐6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140428273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dynamics of microRNAs level associated with pathological venous angiogenesis in experimental toxic liver fibrosis in rats","authors":"E. Lebedeva, A. Babenka, A. T. Shchastniy","doi":"10.17816/gc622891","DOIUrl":"https://doi.org/10.17816/gc622891","url":null,"abstract":"BACKGROUND: It is known that miRNAs are important in liver fibrogenesis. Studies regarding the role of miRNAs in pathological angiogenesis and sinusoid capillarization are insufficient. \u0000AIM: to study the molecular targets (miRNAs and mRNAs) dynamics of associated with pathological angiogenesis in toxic fibrosis of the liver; to evaluate the relationship of the selected molecular factors to the processes of restructuring the intrahepatic vascular system. \u0000METHODS: Fibrosis and subsequent cirrhosis of the liver in rats of the Wistar line (males) were induced for 17 weeks by a freshly prepared solution of thioacetamide. The level of miRNA-19а-3р, miRNA-29b-3р, miRNA-29b-1-5p, miRNA-34b-5р, miRNA-125b-5р, miRNA-130a-5p, miRNA-195-5р, miRNA-449а-5р, miRNA-449с-5р, miRNA-466d, miRNA-489-3р, miRNA-495, miRNA-664-3р, miRNA-3085, miRNA-3558-3р in fresh frozen liver samples, was determined by Two-tailed RT-qPCR. \u0000RESULTS: A change in the profile of targeted miRNAs was established during the initiation and progression of toxic fibrosis. The statistically significant decrease in the level of the miRNA-195-5p and miRNA-664-3p is registered compared to the control point 3 weeks of the experiment, as well as a symmetrical decrease in the level of Vegfa and Ang genes. An increase in the amount of veins is associated with a decrease in the level of miRNA-3585-3p and mRNA Cxcl12, as well as an increase in the area of cells CK19+ in the bile ducts. \u0000CONCLUSION: A joint analysis of morphological and molecular parameters allowed us to suggest that pathological angiogenesis in the toxic model of fibrosis does not proceed the same for arteries, veins and sinusoids. At the same time, Vegfa is probably involved in venous angiogenesis. Despite the decrease in the mRNA level compared to the control point, starting at the stage of portal fibrosis (3 weeks of experiment), its partial recovery, statistically significant increase and correlation with an increase in the amount of veins is observed. Perhaps, against the background of general depression of the synthesis of mRNA with the development of toxic fibrosis, the level of the Vegfa mRNA remains sufficient to stimulate pathological venous angiogenesis. The dynamics of mRNA Ang can be associated with the angiogenesis of the arteries and the capillarization of sinusoids.","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"74 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140434287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUDDEN CARDIAC DEATH IN YOUNG ATHLETES: EXOME SEQUENCING RESULTS","authors":"R.V. Deev, Anastasia Kadykova, Marina Shilova, EI Sharova, Irina Fedyushkina, NA Kulemin, A. Zholinsky","doi":"10.17816/gc569201","DOIUrl":"https://doi.org/10.17816/gc569201","url":null,"abstract":"Ranking risks and prevention of sudden cardiac death in professional young athletes is one of the important unresolved problems in sports medicine. Intense physical exertion can lead to adaptive changes in the cardiovascular system, which can mask some inherited diseases with predominant myocardial involvement, such as hypertrophic cardiomyopathy. Undiagnosed cases of such diseases can be a risk factor for fatal outcomes associated with training and competitive activities, making this problem extremely relevant. \u0000The aim was to conduct a diagnostic search for possible molecular causes of cardiovascular diseases associated with a high risk of sudden death in young athletes. \u0000Methods. Whole-exome sequencing of DNA extracted from two groups of biomaterials was performed: 9 autopsy samples of heart tissues from young athletes who died during intense physical exertion, and 3 samples of venous blood from active athletes of the Russian national teams. The obtained data were subjected to bioinformatic analysis and clinical interpretation. \u0000Results. A total of 12 DNA samples were analyzed using a panel of 277 genes associated with the development of cardiovascular diseases with a high risk of sudden death. In 4 out of 12 samples (33.3%), variants likely related to the phenotype were found upon clinical interpretation of the sequencing results. A pathogenic variant was found in the MYBPC3 gene, leading to the development of hypertrophic cardiomyopathy (OMIM: 115197), and a likely pathogenic variant was found in the TRPM4 gene, associated with progressive familial heart block type IB (OMIM: 618531). Two variants with uncertain clinical significance were also found in the CAV3 and SCN1B genes. \u0000Conclusion. Currently, data from high-throughput sequencing are being accumulated to search for the molecular basis of cardiovascular diseases with a high risk of sudden cardiac death. Identifying young athletes who are carriers of pathogenic and likely pathogenic gene variants is an effective measure for preventing fatal outcomes and personalizing medical support for professional athletes.","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"63 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140451024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PERIODIZATION OF ADAPTATION-COMPENSATORY REMODELING OF BRAIN STRUCTURES IN INCOMPLETE PERMANENT CEREBRAL HYPOPERFUSION IN RATS","authors":"I. V. Gaivoronskiy, V. Chrishtop, V. G. Nikonorova, Alexey A. Semenov, Yulia Alexandrovna Khrustaleva","doi":"10.17816/gc492252","DOIUrl":"https://doi.org/10.17816/gc492252","url":null,"abstract":"Bilateral one-stage ligation of the common carotid arteries in rats is the most common way to form prolonged cerebral hypoxia with cognitive impairment. Early postoperative periods, up to 3 x days, are most commonly used for pharmacological studies. They are characterized by neuronal death, development of hypoenergetic state and edema. In the acute period - 3-8 days, the changes are associated with the activation of astrocytes, which form intercellular cooperation between the neuron, hemocapillary and respiratory burst of neutrophil granulocytes. The permeability of the blood-brain barrier increases. This is accompanied by death of one part of neurons and improvement of vitality of another part. The subacute period from 8 days to 8 weeks is accompanied by death of neurons in a state of poor life support, activation of microglia, myelin fibers damage, increase in the diameter of paravertebral arteries - in the early period, and the development of astrocytosis and angiogenesis - in the late period, which leads to the growth of lipid peroxidation, secondary damage and neuronal death. In the late period, neurodystrophic changes appear, minor neuronal apoptosis and increased permeability of the blood-brain barrier persist. The surviving neurons show metabolic activation and concentration of pericarions near the hemocapillaries.","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"532 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140472633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MITOCHONDRIAL RESPIRATION OF A PRIMARY MIXED CULTURE OF NEURONS FROM HIPPOCAMPUS AT VARIOUS STAGES OF DIFFERENTIATION","authors":"A. S. Zelentsova, Alina Yur'evna Borisova, Veronika Sergeevna Shmigerova, Marina Yur'evna Skorkina, Alexey Deykin","doi":"10.17816/gc529662","DOIUrl":"https://doi.org/10.17816/gc529662","url":null,"abstract":"BACKGROUND: Primary mixed culture of neurons is often used to evaluate the underlying molecular mechanisms of neurodegenerative disorders. However, the isolation of cells from the brain is accompanied by profound changes in cell morphology, behavior, metabolic rate due to enzymatic disintegration and changes in the microenvironment for cells. In this regard, it is relevant to study the basal respiration of mitochondria of neurons, as an indicator of the formation of the functional activity of the cell.AIM: to evaluate the mitochondrial respiration of a primary mixed culture of hippocampal neurons from embryos on the 18th day of gestation (E18) and 2-day-old pups at various stages of differentiation. \u0000METHODS: Primary embryonic (on the 18th day of gestation) and postnatal (on the 2nd day after birth) neuroglial culture of the CD1 mouse hippocampus was used in the work. The functional parameters of cell metabolism were measured by the Agilent analyzer (USA). The rate of the oxygen consumption was calculated based on the results of which of the profile of mitochondrial respiration of the primary mixed culture was built during its differentiation. \u0000RESULTS: Mitochondrial respiration in the postnatal hippocampus fully corresponds to the embryonic hippocampus. The oxidation rate increased almost 2-fold in the embryonic culture of hippocampal neurons, and an increase in metabolic potential was observed as cells differentiated in culture from 2 to 11 days. Neurons of the postnatal culture during differentiation showed a significant decrease in the rate of acidification of the medium by ~4.5 times against the background of a practically unchanged rate of oxidation, which indicates a decrease in the metabolic potential of the culture in the process of maturation. \u0000CONCLUSION: The results obtained prove that hippocampus can be used to study the role of mitochondria in neurogenesis.","PeriodicalId":504619,"journal":{"name":"Genes & Cells","volume":"20 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140478726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}