A5086949282- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Mesenchymal stem cell research
- Cancer-related gene regulation
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Retinoids in leukemia and cellular processes
- Clusterin in disease pathology
- RNA regulation and disease
- Erythrocyte Function and Pathophysiology
- Cancer-related molecular mechanisms research
- Zebrafish Biomedical Research Applications
- Chemokine receptors and signaling
- Angiogenesis and VEGF in Cancer
- Toxic Organic Pollutants Impact
The University of Tokyo
2019-2024
Institute for Stem Cell Biology and Regenerative Medicine
2023-2024
Chiba University
2016-2023
Regenerative Medicine Institute
2019
Tokyo University of Science
2019
Tokyo Medical University
2019
Japan Science and Technology Agency
2007-2013
Centre for Research in Engineering Surface Technology
2012
University of Tsukuba
2007-2009
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is known to mediate wide variety of pharmacological and toxicological effects caused by polycyclic aromatic hydrocarbons. Recent studies have revealed that AhR involved in the normal development homeostasis many organs. Here, we demonstrate knockout (AhR KO) mice are hypersensitive lipopolysaccharide (LPS)-induced septic shock, mainly due dysfunction their macrophages. In response LPS, bone marrow-derived macrophages...
Abstract Hematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here, we present an integrated analysis of transcriptome and chromatin accessibility aged HSCs downstream progenitors. Alterations in preferentially take place aging, which gradually resolve differentiation. Differentially open accessible regions (open DARs) are enriched for enhancers show enrichment binding motifs the STAT, ATF, CNC family transcription factors that activated response to external...
Hematopoietic stem cells (HSCs) exhibit functional alterations, such as reduced regenerative capacity and myeloid-biased differentiation, with age. The HSC niche, which is essential for the maintenance of HSCs, also undergoes marked changes aging. However, it has been technically challenging to directly evaluate contribution niche aging age-associated alterations without niche-damaging myeloablation in transplantation assays. We herein transplanted an excess aged HSCs into young mice...
Abstract Both EZH2 and its homolog EZH1 function as histone H3 Lysine 27 (H3K27) methyltransferases repress the transcription of target genes. Dysregulation H3K27 trimethylation (H3K27me3) plays an important role in development progression cancers such hepatocellular carcinoma (HCC). This study investigated relationship between expression EZH1/2 level H3K27me3 HCC. Additionally, cell growth, tumorigenicity, resistance to sorafenib were also analyzed. lentiviral knockdown pharmacological...
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates diverse dioxin toxicities. Despite mediating the adverse effects, <i>AhR</i> gene conserved among animal species, suggesting important physiological functions for AhR. In fact, recent study revealed AhR has an intrinsic function in female reproduction, though its role male reproduction largely unknown. this study, we show age-dependent regression of seminal vesicles, probably together...
Abstract Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) cancer presents an extremely high-methylation epigenotype this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. analysed epigenetic alterations induced by especially...
Abstract Dihydroorotate dehydrogenase (DHODH) catalyzes a rate-limiting step in de novo pyrimidine nucleotide synthesis. DHODH inhibition has recently been recognized as potential new approach for treating acute myeloid leukemia (AML) by inducing differentiation. We investigated the efficacy of PTC299, novel inhibitor, myelodysplastic syndrome (MDS). PTC299 inhibited proliferation MDS cell lines, and this was rescued exogenous uridine, which bypasses In contrast to AML cells, inefficient at...
The aryl hydrocarbon receptor (AhR) repressor (AhRR) inhibits the AhR activity. AhRR acts by competing with for heterodimer formation nuclear translocator (Arnt) and preventing AhR.Arnt complex from binding xenobiotic-responsive elements. Here, we report that has three evolutionarily conserved SUMOylation consensus sequences within its C-terminal repression domain Lys-542, Lys-583, Lys-660 at sites are modified SUMO-1 in vivo. Arginine mutation of lysines results a significant reduction...
Metabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking changes over time after rare cells such as hematopoietic stem (HSCs). Here, we aimed identify key enzymes that define differences glycolytic metabolism between steady-state conditions murine HSCs elucidate their regulatory mechanisms. Through quantitative 13 C flux analysis glucose using high-sensitivity tracing...
Purpose of review The development new antiaging medicines is great interest to the current elderly and aging population. Aging hematopoietic system attributed stem cells (HSCs), epigenetic alterations are key effectors driving HSC aging. Understanding epigenetics holds promise providing insights for combating age-related hematological malignancies. Recent findings characterized by progressive loss physiological integrity, leading impaired function increased vulnerability death. During aging,...
Werner syndrome (WS), also known as adult progeria, is characterized by accelerated aging symptoms from a young age. Patients with WS experience painful intractable skin ulcers calcifications in their extremities, subcutaneous lipoatrophy, and sarcopenia. However, there no significant abnormality the trunk skin, where fat relatively accumulates. The cause of such differences between limbs unknown. To investigate underlying mechanism behind these phenomena, we established analyzed dermal...
Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic and progenitor (HSPC) maintenance, the role non-canonical in hematopoiesis remains elusive. PRC1.1, a PRC1, consists PCGF1, RING1B, KDM2B, BCOR. We recently showed that PRC1.1 insufficiency induced loss PCGF1 or BCOR causes myeloid-biased promotes transformation cells mice. Here we show serves as an epigenetic switch...
Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential universal HLA-null platelet products have stimulated research ex vivo differentiation human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, BCL-XL (MBX). imMKCLs can act as cryopreservable master supply concentrates. However, proliferation rates...
Abstract Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics an important target for anticancer drugs. The inhibition of polymerization or depolymerization was previously targeted exhibited efficacy against solid tumors. novel small molecule PTC596 directly binds tubulin, inhibits polymerization, downregulates MCL‐1, induces p53‐independent apoptosis acute myeloid leukemia cells. We herein investigated...