Yasuhiro Seki

TIF1β regulates the pluripotency of embryonic stem cells in a phosphorylation-dependent manner

Transcription networks composed of various transcriptional factors specifically expressed in undifferentiated embryonic stem (ES) cells have been implicated in the regulation of pluripotency in ES cells. However, the molecular mechanisms responsible for self-renewal, maintenance of pluripotency, and lineage specification during differentiation of ES cells are still unclear. The results of this study demonstrate that a phosphorylation-dependent chromatin relaxation factor, transcriptional intermediary factor–1β (TIF1β), is a unique regulator of the pluripotency of ES cells and regulates Oct3/4–dependent transcription in a phosphorylation-dependent manner. TIF1β is specifically phosphorylated in pluripotent mouse ES cells at the C-terminal serine 824, which has been previously shown to induce chromatin relaxation. Phosphorylated TIF1β is partially colocalized at the activated chromatin markers, and forms a complex with the pluripotency-specific transcription factor Oct3/4 and subunits of the switching defective/sucrose nonfermenting, ATP-dependent chromatin remodeling complex, Smarcad1, Brg-1, and BAF155, all of which are components of an ES-specific chromatin remodeling complex, esBAF. Phosphorylated TIF1β specifically induces ES cell–specific genes and enables prolonged main-tenance of an undifferentiated state in mouse ES cells. Moreover, TIF1β regulates the reprogramming process of somatic cells in a phosphorylation-dependent manner. Our results suggest that TIF1β provides a phosphorylation-dependent, bidirectional platform for specific transcriptional factors and chromatin remodeling enzymes that regulate the cell differentiation process and the pluripotency of stem cells.

Catalytic performance of 11-molybdo-1-vanadophosphoric acid as a catalyst precursor and the optimization of reaction conditions for the oxidation of methane with hydrogen peroxide

Abstract The oxidation of methane with hydrogen peroxide was carried out by using various Keggin-type heteropolyacids and V-containing complexes in trifluoroacetic acid anhydride. Among the catalysts tested, H4PV1Mo11O40 as a catalyst precursor catalyzed the selective oxidation into oxygenates most efficiently and showed high efficiency for the utilization of hydrogen peroxide. In addition, the reaction conditions were optimized.

High-yield liquid-phase oxygenation of methane with hydrogen peroxide catalyzed by 12-molybdovanadophosphoric acid catalyst precursor

Abstract The title reaction was most efficiently catalyzed by H4PVMo11O40 catalyst precursor in (CF3CO)2O solvent at 353 K. A conversion to the oxygenates such as methylformate and formic acid of 33.0% was achieved.

Prohibitin 2 Regulates the Proliferation and Lineage-Specific Differentiation of Mouse Embryonic Stem Cells in Mitochondria

Background The pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown. Methodology/Principal Findings In this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria. Conclusions/Significance Our results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells.

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

Comparison of catalytic activity and efficiency of hydrogen peroxide utilization for di-iron-containing silicotungstate with those for iron containing complexes and the oxidation of methane and ethane

The Keggin-type di-iron-substituted γ-SiW10{Fe(OH2)}2O386- showed high efficiency of hydrogen peroxide utilization for the oxidation of cyclohexane. The efficiency and catalytic activity greatly depended on the structures of the iron centers. Such a structure dependency of the catalysis is significant and the remarkable catalytic performance of di-iron-substituted polyoxometalate may be related to the catalysis by methane monooxygenase. Not only cyclohexane but also cyclooctane, n-hexane, n-pentane, and adamantane were catalytically oxygenated with high efficiency of hydrogen peroxide utilization. Even methane and ethane were oxidized. It was also demonstrated that the potassium salt of γ-SiW10{Fe(OH2)}2O386- oxidized methane in water.

Lipase member H frequently overexpressed in human esophageal adenocarcinomas.

Esophageal cancer is one of the most frequent causes of cancer-related deaths worldwide. This is due to its asymptomatic nature or mild nonspecific symptoms. Most patients are diagnosed after appearance of prominent symptoms, and tumors are frequently accompanied by severe infiltration. Therefore, molecular biomarkers for the prognosis of early-stage esophageal cancer are desired. In this study, we examined the prognostic potential of lipase H (LIPH), a recently reported biomarker for lung adenocarcinoma and squamous carcinoma. We found that LIPH mRNA is also frequently upregulated in esophageal adenocarcinoma. Immunohistochemical analysis confirmed LIPH protein expression in various esophageal tumor tissue sections. Interestingly, higher expression of LIPH in esophageal adenocarcinoma showed a positive correlation with longer survival of patients. Our data suggest that LIPH may have prognostic value for esophageal cancer.

Proteomic Analysis of Mouse ES Cells

Embryonic stem (ES) cells have generated enormous interest because of their capacity to self-renew and differentiate into various cell types in vitro. Although numerous problems are encountered in the use of ES cells for regenerative medicine, such as ethical issues associated with the use of stem cells established from terminated human embryos and immunorejection due to transplantation of allogenic ES cell-derived cells into patients, recent technologies to generate induced pluripotent stem (iPS) cells from adult somatic cells have provided alternative ways to access pluripotent stem cells (Takahashi et al., 2007). However, the practical application of these pluripotent stem cells has yet to emerge, and regulatory mechanisms are not well known. Moreover, precise differentiation methodologies of ES and iPS cells have not been developed. These problems cause difficulties in the manipulation of pluripotent stem cells and derivation of functionally differentiated cells. Detailed analysis of the transcriptome has allowed elucidation of transcription networks that regulate the pluripotency of these stem cells. However, the specific nuclear infrastructures that maintain the pluripotent stem cell-specific transcription network have not yet been elucidated. We used proteomics to analyze the nuclear protein machinery in stem cells and identified some crucial components for the maintenance of pluripotent stem cells. In addition, various growth factors and extracellular matrix components regulate the pluripotency and differentiation of stem cells. Therefore, the cell surface receptors that bind these regulatory factors are important for the precise regulation of stem cells. We have also explored stem cell-specific cellsurface markers by proteomic analysis of mouse ES cells. These cell-surface membrane proteins can be useful to manipulate pluripotent stem cells. In this chapter, we describe some examples of new findings elucidated by proteomic analysis of ES cells.

Low-temperature oxygenation of methane into formic acid withmolecular oxygen in the presence of hydrogen catalysed byPd0.08Cs2.5H1.34PVMo11O40

The title reaction is catalysed by Pd 0.08 Cs 2.5 H 1.34 PVMo 11 O 4 0 at temperatures as low as 423–593 K, and the catalytic rate, which reached a maximum at 573 K, is 1.2 × 10 - 4 mol h - 1 g - 1 , ca. 3 × 10 2 times higher than FePO 4 , the most active catalyst previously reported.