A5040988695- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Pancreatic function and diabetes
- Multiple Myeloma Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- Chronic Myeloid Leukemia Treatments
- Pluripotent Stem Cells Research
- Cardiac Ischemia and Reperfusion
- Acute Lymphoblastic Leukemia research
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Kruppel-like factors research
- Peripheral Neuropathies and Disorders
- Platelet Disorders and Treatments
- Barrier Structure and Function Studies
Chiba University
2013-2023
Japan Science and Technology Agency
2010-2016
Kumamoto University
2011
Kobe University
2004
Hokkaido University
2004
Side population (SP) cell analysis and sorting have been successfully applied to hepatocellular carcinoma (HCC) lines identify a minor with cancer stem properties. However, the molecular mechanisms operating in SP cells remain unclear. The polycomb gene product BMI1 plays central role self-renewal of somatic variety tissues organs seems be implicated tumor development. In this study, we determined critical maintenance phenotype HCC lines. was preferentially expressed Huh7 PLC/PRF/5 compared...
Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently patients with myelodysplastic disorders including syndromes (MDSs) MDS/myeloproliferative neoplasm (MPN) overlap (MDS/MPN). In our patient cohort, were also found often coincided tet methylcytosine dioxygenase 2 (TET2) mutations. Consistent these...
Glucose-induced insulin secretion from pancreatic β-cells depends critically on ATP-sensitive K+ channel (KATP channel) activity, but it is not known whether KATP channels are involved in the potentiation of by glucose-dependent insulinotropic polypeptide (GIP). In mice lacking (Kir6.2−/− mice), we found that pretreatment with GIP vivo failed to blunt rise blood glucose levels after oral load. Kir6.2−/− mice, was markedly attenuated, indicating essential effect GIP. contrast, glucagon-like...
Abstract Recent advances in stem cell biology have identified tumor‐initiating cells (TICs) a variety of cancers including hepatocellular carcinoma (HCC). Polycomb group gene products such as BMI1 and EZH2 been characterized general self‐renewal regulators wide range normal TICs. We previously reported that Ezh2 tightly regulates the differentiation murine hepatic stem/progenitor cells. However, role HCC remains unclear. In this study, we conducted loss‐of‐function assay using short‐hairpin...
Tumor-initiating cells (TICs) play a central role in tumor development, metastasis, and recurrence. In the present study, we investigated effect of disulfiram (DSF), an inhibitor aldehyde dehydrogenase, toward tumor-initiating hepatocellular carcinoma (HCC) cells. DSF treatment suppressed anchorage-independent sphere formation both HCC Flow cytometric analyses showed that but not 5-fluorouracil (5-FU) drastically reduces number The assays epithelial cell adhesion molecule (EpCAM)+ co-treated...
Abstract Purpose: EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation H3K27 (H3K27me3) to repress transcription target genes are implicated in pathogenesis various cancers including multiple myeloma prostate cancer. Here, we investigated preclinical effects UNC1999, a dual inhibitor combination with proteasome inhibitors on Experimental Design: In vitro vivo efficacy UNC1999 was evaluated cell lines, primary patient cells, xenograft model....
The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast (TB), and primitive endoderm (PrE). Although embryonic stem cells (ESCs) (TSCs) retain the functional properties epiblast TB, respectively, that fully recapitulate developmental potential PrE have not been established. Here, we report derivation (PrESCs) in mice. PrESCs day 4.5 founder PrE, are efficiently incorporated into upon injection, generate functionally competent PrE-derived tissues, support fetal...
Abstract We previously reported that forced expression of Bmi1 (B lymphoma Moloney murine leukemia virus insertion region 1 homolog) in hepatic stem/progenitor cells purified from fetal liver enhances their self-renewal and drives cancer initiation. In the present study, we examined contribution Ink4a/Arf tumor suppressor gene locus, one major targets , to stem cell expansion −/− Delta-like protein (Dlk)+ showed de-repression locus displayed impaired growth activity. contrast, Dlk+ gave rise...
Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), ability TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing identify somatic mutations in 24 with newly diagnosed phase who were registered JALSG CML212 study. We identified 191 other than BCR-ABL1 fusion gene (median 8, range 1-17). Age, hemoglobin concentration white...
Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an important role in exocytosis. Several potential effectors Rab3, including rabphilin3 Rims (Rim1 Rim2), have been isolated characterized. Noc2 was identified originally endocrine pancreas as molecule homologous to rabphilin3, but its exocytosis unclear. To clarify physiological function directly, we generated knockout (Noc2 -/- ) mice. Glucose intolerance with impaired insulin secretion induced vivo by acute stress...
Recurrent inactivating mutations have been identified in various hematological malignancies the X-linked BCOR gene encoding BCL6 corepressor (BCOR); however, its tumor suppressor function remains largely uncharacterized. We generated mice missing Bcor exon 4, expressing a variant lacking BCL6-binding domain. Although deletion of 4 male (BcorΔE4/y ) compromised repopulating capacity hematopoietic stem cells, BcorΔE4/y thymocytes had augmented proliferative culture and showed strong propensity...
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone methyltransferase G9a and associated with repression of transcription. However, both role significance H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay using short-hairpin RNA pharmacological interference. Knockdown reduced levels impaired HCC cell growth sphere formation. transforming factor β1-induced epithelial mesenchymal transition (EMT) was...
Background The polycomb-group (PcG) proteins function as general regulators of stem cells. We previously reported that retrovirus-mediated overexpression Bmi1, a gene encoding core component polycomb repressive complex (PRC) 1, maintained self-renewing hematopoietic cells (HSCs) during long-term culture. However, the effects Bmi1 on HSCs in vivo remained to be precisely addressed. Methodology/Principal findings In this study, we generated mouse line where can conditionally overexpressed...