A5019166922- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Mesenchymal stem cell research
- Nerve injury and regeneration
- Developmental Biology and Gene Regulation
- Axon Guidance and Neuronal Signaling
- Retinal Development and Disorders
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- Signaling Pathways in Disease
- Congenital heart defects research
- Cold Atom Physics and Bose-Einstein Condensates
- CRISPR and Genetic Engineering
- Quantum, superfluid, helium dynamics
- Tissue Engineering and Regenerative Medicine
- Endoplasmic Reticulum Stress and Disease
- Galectins and Cancer Biology
- Gene Regulatory Network Analysis
- Cytokine Signaling Pathways and Interactions
- Macrophage Migration Inhibitory Factor
- Genetics and Neurodevelopmental Disorders
- Physics of Superconductivity and Magnetism
Keio University Hospital
2001-2025
University of Tsukuba
2025
The University of Tokyo
1993-2023
Keio University
2004-2016
Japan Science and Technology Agency
2002-2008
Bridgestone (Japan)
2006
Tokyo University of Science
2005
University of Calgary
1999-2003
In-Q-Tel
2001
Osaka University
2001
Recent studies have shown that neurogenesis is enhanced after hypoxia and erythropoietin (EPO), an inducible cytokine, produced in the brain as part of intrinsic response. Thus, we asked whether EPO might regulate by forebrain neural stem cells (NSCs). We found receptors are expressed embryonic germinal zone during well adult subventricular zone, which continues to generate neurons throughout adulthood. Cultured NSCs exposed a modest two- threefold more neurons, was associated with elevation...
Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These were lost following differentiation, replaced by the expression neuron-, glial-, smooth muscle cell–, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to truncus arteriosus outflow tract contributed dorsal root...
Hes1 is one of the basic helix-loop-helix transcription factors that regulate mammalian CNS development, and its loss- gain-of-function phenotypes indicate it negatively regulates neuronal differentiation. Here we report Hes1(-/-) mice expressed both early (TuJ1 Hu) late (MAP2 Neurofilament) markers prematurely, there were approximately twice normal number neurons in brain during neural development. However, immunochemical analyses sections dissociated cells using progenitor markers,...
The cytokines that signal through the common receptor subunit gp130, including ciliary neurotrophic factor (CNTF), interleukin-6, leukemia inhibitory (LIF) and oncostatin M, have pleiotropic functions in CNS development. Given restricted expression domain of CNTF α (CNTFR) developing forebrain germinal zone adult periventricular area, we examined putative role CNTFR/LIFR/gp130-mediated signaling regulating neural stem cell fate <i>in vivo</i> vitro</i>. Analysis of<i>LIFR</i>-deficient mice...
Abstract Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of cord, especially inflammatory cytokines dramatically increase acute phase at site, is considered be an important cause inhibitory mechanism neuronal differentiation following SCI. Interleukin‐6 (IL‐6), which has demonstrated induce NSPCs undergo astrocytic...
Abstract Transplantation of human neural stem cells (NSCs) is a promising potential therapy for neurologic dysfunctions after the hyperacute stage stroke in humans, but large amounts NSCs must be expanded long‐term culture such therapy. To determine their possible therapeutic stroke, fetal stem/progenitor (NSPCs) (i.e., neurosphere‐forming cells) were isolated originally from forebrain tissues one fetus, and neurosphere (exceeding 24 weeks), then xenografted into lesioned areas brains...
Abstract Neural stem/progenitor cells (NS/PCs) can generate a wide variety of neural cells. However, their fates are generally restricted, depending on the time and location NS/PC origin. Here we demonstrate that recapitulate spatiotemporal regulation central nervous system (CNS) development in vitro by using neurosphere-based culture embryonic stem (ES) cell-derived NS/PCs. This ES neurosphere enables efficient derivation highly neurogenic fibroblast growth factor-responsive NS/PCs with...
Glycoprotein130 (gp130) and Notch signaling are thought to participate in neural stem cell (NSC) self-renewal. We asked whether gp130 regulates activity forebrain epidermal growth factor (EGF)-responsive NSCs. Disruption of Notch1 using antisense or a gamma-secretase inhibitor demonstrated requirement for the maintenance proliferation Ciliary neurotrophic (CNTF) activation NSCs rapidly increased expression. NOTCH1 activation, indicated by tumor necrosis alpha-converting enzyme (TACE)-...
In the subventricular zone of adult mammalian forebrain, neural stem cells (NSCs) reside and proliferate to generate young neurons. We screened factors that promoted proliferation NSCs in vitro by a recently developed proteomics technique, ProteinChip system. this screen, we identified soluble carbohydrate-binding protein, Galectin-1, as candidate. show herein Galectin-1 is expressed subset slowly dividing astrocytes, which includes NSCs. Based on results from intraventricular infusion...
Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) play a central role stimulation of feeding. They sense and integrate peripheral signals, including ghrelin leptin. However, mechanisms interaction these hormones NPY are largely unknown. This study explored underlying signaling cross talk between leptin neurons. Cytosolic Ca(2+) concentration ([Ca(2+)](i)) single isolated from ARC adult rats was measured by fura-2 microfluorometry. Ghrelin increased [Ca(2+)](i) 31% The...
The transcription factor Sox2 is expressed at high levels in neural stem and progenitor cells. Here, we inactivated specifically the developing brain by using Cre–loxP system. Although mutant animals did not survive after birth, analysis of late gestation embryos revealed that loss causes enlargement lateral ventricles a decrease number neurosphere‐forming However, although their neurogenic potential attenuated, Sox2‐deficient cells retain multipotency self‐renewal capacity. We found...
Abstract Despite recent progress in the neural stem cell biology, their cellular characteristics have not been described well. We investigated various of cells (NSCs) vivo during CNS development, using FACS to identify NSCs. first examined stage‐dependent changes physical parameters, forward scatter (FSC) and side (SSC) profiles, NSCs from developing striatum, where they appear be active throughout life mammals. were divided into several fractions according FSC/SSC profile. With number...
Significance Neural stem/progenitor cells (NSPCs) restrict their differentiation potential by developmental stage-dependent temporal specification. Thereby, specific and efficient induction of homogeneous target cell populations remains a challenge in stem biology. Here, we provided solution identifying the molecular machinery responsible for neurogenic-to-gliogenic transition NSPCs, process termed “competence change.” We identified microRNA-17/106–p38 axis as critical regulator competence...
Mammalian neural stem/progenitor cells (NSPCs) sequentially generate neurons and glia during CNS development. Here we identified miRNA-153 (miR-153) as a modulator of the temporal regulation NSPC differentiation. Overexpression (OE) miR-153 delayed onset astrogliogenesis maintained NSPCs in an undifferentiated state vitro developing cortex. The transcription factors nuclear factor I (NFI) A B, essential regulators initiation gliogenesis, were found to be targets miR-153. Inhibition early...
Neurogenesis in specific brain regions adult mammals decreases with age. Progressive reduction the proliferation of neural stem and progenitor cells (NS/PCs) is a primary cause this age-associated decline. However, mechanism responsible for poorly understood. We identify p38 MAPK as key factor (NPCs) neurogenic niches. expression NS/PCs downregulated during aging. Deletion p38α specifically reduces NPCs but not cells. Conversely, forced aged mouse subventricular zone (SVZ) restores NPC...