Histone H3 K4/9/27 trimethylation levels regulate wound healing and stem cell dynamics in adult skin

189 pagesEpigenetic mechanisms controlling adult mammalian stem cell dynamics are critical for tissue homeostasis and injury repair but are poorly understood. Defects in tissue stem cell fate choices give rise to various developmental disorders, malfunctioning of the tissue and cancers. Recent studies identified various epigenetic factors and their modifiers providing insights how the tissue stem cell fate determination is regulated during tissue regeneration. Previously, we found that adult mouse skin and hair follicle stem cells display reduced histone H3 K4me3, K9me3 and K27me3 methylation levels (hypomethylation) at a specific stage of homeostasis, preceding hair growth. To examine the physiological relevance of hypomethylation, we attempt to block it by two different methods; 1) Chemical inhibition of relevant histone demethylases and 2) Making use of a novel transgenic mouse model in which the founder transgenic mouse can subsequently produce progeny with expression of 1 in 10 distinct combinations of 3 relevant histone methyltransferases inducible in the skin epithelium. We demonstrate that interfering with hypomethylation results in subsequent impaired differentiation and growth of hair follicles and delayed wound healing. In wounding, epithelial cell differentiation and blood vessel recruitment were impaired, while epithelial cell proliferation and fibroblast recruitment were unaffected. The phenotypes associated with blocked hypomethylation are accompanied by increased BMP4 expression and selective H3 K4me3 up-regulation on the BMP4 promoter, which is known to regulate HFSC quiescence, hair cycle, and injury repair. In addition, we characterize genetic labeling tools new to skin, Aspm-CreER, and mark a major long-term self-renewing population of epidermal-specific stem cells. With these, and previously characterized Lgr5-CreER tools for the hair follicle, we demonstrate reduced contribution of epithelial SC lineages to wound healing after interfering with hypomethylation. Our results suggest that hypomethylation of histone H3 K4/9/27me3 at a specific stage of homeostasis is essential for adult skin epithelial SC dynamics for proper tissue homeostasis and repair

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients. Results In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2. Conclusions We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment

Growth and Reform in the Korean Economy Proceedings of the Conference on Growth and Reform in Korea - Implications for Australia

This paper explores the issue of outward foreign direct investment (OFDI) exporting Korean jobs during 9862003. In the midst of an overall increase in employment in Korea, there was a temporally coincident increase in OFDI and a decline in manufacturing employment. An examination of the employment structure and capital stock changes suggests that there had been a structural transition in the Korean economy from a capital intensive to a knowledge intensive base. Simple regression analyses demonstrated that the OFDI from Korea had a checking effect on rising unemployment. As such, the increase in unemployment can be attributed to the trends of the time and the East Asian financial crisis.Growth refrom, Korea, Australia, OFDI, Outward foreign direct investment, Employment, capital stock, incentive base, East Asian Financial Crisis

Growth and Reform in the Korean Economy. Proceedings of the Conference on Growth and Reform in Korea: Implications for Australia

This paper explores the issue of outward foreign direct investment (OFDI) exporting Korean jobs during 1986–2003. In the midst of an overall increase in employment in Korea, there was a temporally coincident increase in OFDI and a decline in manufacturing employment. An examination of the employment structure and capital stock changes suggests that there had been a structural transition in the Korean economy from a capital intensive to a knowledge intensive base. Simple regression analyses demonstrated that the OFDI from Korea had a checking effect on rising unemployment. As such, the increase in unemployment can be attributed to the trends of the time and the East Asian financial crisis.

Integrative analysis of multi-omics data for identifying multi-markers for diagnosing pancreatic cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Background microRNA (miRNA) expression plays an influential role in cancer classification and malignancy, and miRNAs are feasible as alternative diagnostic markers for pancreatic cancer, a highly aggressive neoplasm with silent early symptoms, high metastatic potential, and resistance to conventional therapies. Methods In this study, we evaluated the benefits of multi-omics data analysis by integrating miRNA and mRNA expression data in pancreatic cancer. Using support vector machine (SVM) modelling and leave-one-out cross validation (LOOCV), we evaluated the diagnostic performance of single- or multi-markers based on miRNA and mRNA expression profiles from 104 PDAC tissues and 17 benign pancreatic tissues. For selecting even more reliable and robust markers, we performed validation by independent datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) data depositories. For validation, miRNA activity was estimated by miRNA-target gene interaction and mRNA expression datasets in pancreatic cancer. Results Using a comprehensive identification approach, we successfully identified 705 multi-markers having powerful diagnostic performance for PDAC. In addition, these marker candidates annotated with cancer pathways using gene ontology analysis. Conclusions Our prediction models have strong potential for the diagnosis of pancreatic cancer