Publications by authors named "Yasuhito Tokumoto"

Memory T cells are crucial players in vertebrate adaptive immunity but their development is incompletely understood. Here, we describe a method to produce human memory-like T cells from naive human T cells in culture. Using commercially available human T-cell differentiation kits, both purified naive CD8+ T cells and purified naive CD4+ T cells were activated via T-cell receptor signaling and appropriate cytokines for several days in culture.

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The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal.

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Heme oxygenase (HO) is a mono-oxygenase utilizing heme and molecular oxygen (O) as substrates to generate biliverdin-IXα and carbon monoxide (CO). HO-1 is inducible under stress conditions, while HO-2 is constitutive. A balance between heme and CO was shown to regulate cell death and survival in many experimental models.

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CO is a gaseous mediator generated by HO. Our previous studies revealed that CO generated from inducible HO-1 or from constitutive HO-2 modulates function of different heme proteins or enzymes through binding to their prosthetic ferrous heme to alter their structures, regulating biological function of cells and organs. Such CO-directed target macromolecules include sGC and CBS.

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Cell transplantation therapy with oligodendrocyte precursor cells (OPCs) is a promising and effective treatment for diseases involving demyelination in the central nervous system (CNS). In previous studies, we succeeded in producing O4(+) oligodendrocytes (OLs) from mouse- and human-induced pluripotent stem cells (iPSCs) in vitro; however, the efficiency of differentiation into OLs was lower for iPSCs than that for embryonic stem cells (ESCs). To clarify the cause of this difference, we compared the expression of proteins that contribute to OL differentiation in mouse iPSC-derived cells and in mouse ESC-derived cells.

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Induced pluripotent stem cells (iPSCs) prepared from somatic cells might become a novel therapeutic tool in regenerative medicine, especially for the central nervous system (CNS). In this study, we attempted to induce O4-positive (O4(+)) oligodendrocytes from adult human fibroblast-derived iPSCs in vitro. We used two adult human iPSC cell lines, 201B7 and 253G1.

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Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and defects in these cells can result in CNS dysfunction. Although oligodendrocyte precursor cell (OPC) transplantation therapy is an effective cure for several disorders, there is no readily available source of these cells. Recent studies have described the generation of induced pluripotent stem cell (iPSC) from somatic cells, leading to speculation that this technique might become a novel therapeutic tool in regenerative medicine.

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Background: The investigation of network dynamics is a major issue in systems and synthetic biology. One of the essential steps in a dynamics investigation is the parameter estimation in the model that expresses biological phenomena. Indeed, various techniques for parameter optimization have been devised and implemented in both free and commercial software.

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Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and defects in these cells can result in the loss of CNS functions. Although oligodendrocyte progenitor cells transplantation therapy is an effective cure for such symptoms, there is no readily available source of these cells. Recent studies have described the generation of induced pluripotent stem cells (iPS cells) from somatic cells, leading to anticipation of this technique as a novel therapeutic tool in regenerative medicine.

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To match the demand of regenerative medicine for nerve system, collection of stem cells from the post-mortem body is one of the most practical ways. In this study, the storage condition of the post-mortem body was examined. We prepared neural stem/progenitor cells (NSPCs) from post-mortem rat brains stored at different temperatures.

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only causes apoptotic cell death in tumor cells, but also activates some transcription factors and affects several other cellular functions. In this study, we observed the effect of administration of TRAIL on gene expression downstream of the cyclic AMP responsive element (CRE) enhancer by using the signal transduction reporter cis-element plasmid pCRE-d2EGFP. Western blotting showed that after administration of TRAIL, the expression level of reporter protein d2EGFP was down-regulated in NIH3T3 cells.

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Thyroid hormone induces differentiation of many different tissues in mammals, birds, and amphibians. The different tissues all differentiate from proliferating precursor cells, and the normal cell cycle is suspended while cells undergo differentiation. We have investigated how thyroid hormone affects the expression of the E2F-1 protein, a key transcription factor that controls G1- to S-phase transition.

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The timing of oligodendrocyte development is regulated by thyroid hormone (TH) in vitro and in vivo, but it is still uncertain which TH receptors mediate this regulation. TH acts through nuclear receptors that are encoded by two genes, TRalpha and TRbeta. Here, we provide direct evidence for the involvement of the TRalpha1 receptor isoform in vivo, by showing that the number of oligodendrocytes in the postnatal day 7 (P7) and P14 optic nerve of TRalpha1-/- mice is decreased compared with normal.

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A cell-intrinsic timer helps control when rodent oligodendrocyte precursor cells (OPCs) exit the cell cycle and terminally differentiate when cultured in platelet-derived growth factor (PDGF) and thyroid hormone (TH). There is evidence that the cyclin-dependent kinase inhibitor (CKI) p27/Kip1 (p27) is a component of this TH-regulated timer, as it increases as OPCs proliferate and is required for the timer to operate accurately. Here, we provide evidence that another CKI, p18/INK (p18), may also be a component of the timer: it increases as OPCs proliferate, and its overexpression in OPCs accelerates the timer, causing the cells to differentiate prematurely.

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