• 한국동물번식학회:학술대회논문집
• /
• 한국동물번식학회 2001년도 발생공학 국제심포지움 및 학술대회 발표자료집
• /
• pp.25-31
• /
• 2001

During early development, a dramatic reduction in methylation levels occurs in mouse (Monk et al., 1987). The process of epigenetic reprogramming in early embryos erases gamete-specific methylation patterns inherited from the parents (Howlett ＆ Reik 1991, Monk et al., 1987, Oswald et al., 2000, Sanford et al., 1984). This genome-wide demethylation process may be a prerequisite for the formation of pluripotent stem cells that are important for the later development (Reik ＆ Surani 1997). During post-implantation development, a wave of de novo methylation takes place; most of the genomic DNA is methylated at defined developmental timepoints, whereas tissue-specific genes undergo demethylation in their tissues of expression (Kafri et al., 1992, Razin ＆ Kafri 1994). Another demethylation-remethylation cycle of epigenetic reprogramming takes place during gametogenesis and is necessary for resetting of genomic imprinting (Solter 1988). The dynamic epigenetic reprogramming events appear to be basic and are probably conserved in eutherian mammals (see below). (omitted)

• Molecules and Cells
• /
• 제42권3호
• /
• pp.189-199
• /
• 2019

Cell-to-cell variability in gene expression exists even in a homogeneous population of cells. Dissecting such cellular heterogeneity within a biological system is a prerequisite for understanding how a biological system is developed, homeostatically regulated, and responds to external perturbations. Single-cell RNA sequencing (scRNA-seq) allows the quantitative and unbiased characterization of cellular heterogeneity by providing genome-wide molecular profiles from tens of thousands of individual cells. A major question in analyzing scRNA-seq data is how to account for the observed cell-to-cell variability. In this review, we provide an overview of scRNA-seq protocols, computational approaches for dissecting cellular heterogeneity, and future directions of single-cell transcriptomic analysis.

• 대한의생명과학회지
• /
• 제26권3호
• /
• pp.238-243
• /
• 2020

Tuberculosis is a global public health problem and manifests itself as a difference in the genetic susceptibility of the host, along with the properties of Mycobacterium tuberculosis (MTB). The single nucleotide polymorphisms (SNPs) and candidate genes proposed in the Genome-wide association study (GWAS) on tuberculosis in a recently published Chinese population were reported. In this study, we investigated whether the genetic polymorphism of candidate genes related to tuberculosis is reproduced when targeting Koreans. The CLCN6 (rs12404124, rs198391, rs535107), DOK7 (rs1203104, rs1203103) and HLA-DRA (rs1051336) gene polymorphisms showed statistically significant results. In addition, it was also found whether it acts as an expression quantitative trait loci (eQTL) that can influence gene expression. This study confirmed that the genetic polymorphism of the three genes (CLCN6, DOK7, HLA-DRA) affects the development of tuberculosis and will help to understand the genetic specificity of tuberculosis and the interaction between pathogens and hosts.

• Molecules and Cells
• /
• 제41권12호
• /
• pp.993-999
• /
• 2018

One of the most interesting findings from genome-wide expression analysis is that a considerable amount of noncoding RNA (ncRNA) is present in the cell. Recent studies have identified diverse biological functions of ncRNAs, which are expressed in a much wider array of forms than proteins. Certain ncRNAs associated with diseases, in particular, have attracted research attention as novel therapeutic targets and diagnostic markers. BC200 RNA, a 200-nucleotide ncRNA originally identified as a neuron-specific transcript, is abnormally over-expressed in several types of cancer tissue. A number of recent studies have suggested mechanisms by which abnormal expression of BC200 RNA contributes to the development of cancer. In this article, we first provide a brief review of a recent progress in identifying functions of BC200 RNA in cancer cells, and then offer examples of other ncRNAs as new therapeutic targets and diagnostic markers for human cancer. Finally, we discuss future directions of studies on BC200 RNA for new cancer treatments.

• Biomolecules & Therapeutics
• /
• 제22권2호
• /
• pp.143-148
• /
• 2014

Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권3호
• /
• pp.353-360
• /
• 2017

Several human diseases have been associated with mitochondrial voltage-dependent anion channel-1 (VDAC1) due to its role in calcium ion transportation and apoptosis. Recent studies suggest that VDAC1 may interact with endothelium-dependent nitric oxide synthase (eNOS). Decreased VDAC1 expression may limit the physical interaction between VDAC1 and eNOS and thus impair nitric oxide production, leading to cardiovascular diseases, including pulmonary arterial hypertension (PAH). In this report, we conducted meta-analysis of genome-wide expression data to identify VDAC1 influenced genes implicated in PAH pathobiology. First, we identified the genes differentially expressed between wild-type and Vdac1 knockout mouse embryonic fibroblasts in hypoxic conditions. These genes were deemed to be influenced by VDAC1 deficiency. Gene ontology analysis indicates that the VDAC1 influenced genes are significantly associated with PAH pathobiology. Second, a molecular signature derived from the VDAC1 influenced genes was developed. We suggest that, VDAC1 has a protective role in PAH and the gene expression signature of VDAC1 influenced genes can be used to i) predict severity of pulmonary hypertension secondary to pulmonary diseases, ii) differentiate idiopathic pulmonary artery hypertension (IPAH) patients from controls, and iii) differentiate IPAH from connective tissue disease associated PAH.

• Toxicological Research
• /
• 제26권2호
• /
• pp.137-147
• /
• 2010

Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes ($\geq$ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2), secreted phosphoprotein 1 (Spp1), and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권11호
• /
• pp.5433-5438
• /
• 2012

Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

• Molecules and Cells
• /
• 제45권5호
• /
• pp.306-316
• /
• 2022

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

• 대한한방내과학회지
• /
• 제30권3호
• /
• pp.594-603
• /
• 2009

Objectives : ICH breaks down blood vessels within the brain parenchyma, which finally leads to neuronal loss, drugs to treat ICH have not yet been established. In this experiment, we measured the effect of Woowhangchongshim-won (WWCSW) on intracerebral hemorrhage (ICH) in rat using microarray technology. Methods : We measured the effect of WWCSW on ICH in rat using microarray technology. ICH was induced by injection of collagenase type IV, and total RNA was isolated. Image files of microarray were measured using a ScanArray scanner, and the criteria of the threshold for up- and down-regulation was 2 fold. Hierarchical clustering was implemented using CLUSTER and TREEVIEW program, and for Ontology analysis. GOSTAT program was applied in which p-value was calculated by Chi square or Fisher's exact test based on the total array element. Results : WWCSW-treatment restored the gene expression altered by ICH-induction in brain to the levels of 76.0% and 70.1% for up- and down-regulated genes, respectively. Conclusion : Co-regulated genes by ICH model of rat could be used as molecular targets for therapeutic effects of drug including WWCSW. That is, the presence of co-regulated genes may represent the importance of these genes in ICH in the brain and the change of expression level of these co-regulated genes would also indicate the functional change of brain tissue.