TY - JOUR AU - Biró, Orsolya AU - Nagy, Bálint AU - Rigó, János TI - Identifying miRNA regulatory mechanisms in preeclampsia by systems biology approaches JF - HYPERTENSION IN PREGNANCY J2 - HYPERT PREGN VL - 36 PY - 2017 IS - 1 SP - 90 EP - 99 PG - 10 SN - 1064-1955 DO - 10.1080/10641955.2016.1239736 UR - https://m2.mtmt.hu/api/publication/3152197 ID - 3152197 AB - BACKGROUND: Preeclampsia (PE) is the major cause of maternal and fetal morbidity and mortality, affecting 3-8% of all pregnancies around the globe. miRNAs are small, noncoding RNA molecules, which negatively regulate gene expression. Abnormally expressed miRNAs contribute to pregnancy complications such as PE. The aim of our study was to find possible regulatory mechanisms by system biology approaches, which are connected to the pathogenesis of PE. METHODS: We integrated publicly available miRNA and gene expression profiles and created a network from the significant miRNA-mRNA pairs with the help of MAGIA and Cytoscape softwares. Two subnetworks were expanded by adding protein-protein interactions. Differentially expressed miRNAs were identified for the evaluation of their regulatory effect. We analyzed the miRNAs and their targets using different bioinformatics tools and through literature research. RESULTS: Altogether, 52,603 miRNA-mRNA interactions were generated by the MAGIA web tool. The top 250 interactions were visualized and pairs with q < 0.0001 were analyzed, which included 85 nodes and 80 edges signalizing the connections between 52 regulated genes and 33 miRNAs. A total of 11 of the regulated genes are PE related and 9 of them were targeted by multiple miRNAs. A total of 8 miRNAs were associated with PE before, and 13 miRNAs regulated more than 1 mRNA. Hsa-mir-210 was the highest degree node in the network and its role in PE is well established. CONCLUSIONS: We identified several miRNA-mRNA regulatory mechanisms which may contribute to the pathogenesis of PE. Further investigations are needed to validate these miRNA-mRNA interactions and to enlighten the possibilities of developing potential therapeutic targets. LA - English DB - MTMT ER - TY - JOUR AU - Roost, Matthias S. AU - Slieker, Roderick C. AU - Bialecka, Monika AU - van, Iperen Liesbeth AU - Fernandes, Maria M. Gomes AU - He, Nannan AU - Suchiman, H. Eka D. AU - Szuhai, Károly AU - Carlotti, Francoise AU - de, Koning Eelco J. P. AU - Mummery, Christine L. AU - Heijmans, Bastiaan T. AU - Lopes, Susana M. Chuva de Sousa TI - DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 8 PY - 2017 PG - 11 SN - 2041-1723 DO - 10.1038/s41467-017-01077-3 UR - https://m2.mtmt.hu/api/publication/34794192 ID - 34794192 N1 - Export Date: 22 April 2024 AB - Determining cell identity and maturation status of differentiated pluripotent stem cells (PSCs) requires knowledge of the transcriptional and epigenetic trajectory of organs during development. Here, we generate a transcriptional and DNA methylation atlas covering 21 organs during human fetal development. Analysis of multiple isogenic organ sets shows that organ-specific DNA methylation patterns are highly dynamic between week 9 (W9) and W22 of gestation. We investigate the impact of reprogramming on organ-specific DNA methylation by generating human induced pluripotent stem cell (hiPSC) lines from six isogenic organs. All isogenic hiPSCs acquire DNA methylation patterns comparable to existing hPSCs. However, hiPSCs derived from fetal brain retain brain-specific DNA methylation marks that seem sufficient to confer higher propensity to differentiate to neural derivatives. This systematic analysis of human fetal organs during development and associated isogenic hiPSC lines provides insights in the role of DNA methylation in lineage commitment and epigenetic reprogramming in humans. LA - English DB - MTMT ER -