A5088573439- Pluripotent Stem Cells Research
- Parkinson's Disease Mechanisms and Treatments
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neural Engineering
- Genetic Neurodegenerative Diseases
- Nerve injury and regeneration
- Nuclear Receptors and Signaling
- Neurological disorders and treatments
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Tissue Engineering and Regenerative Medicine
- Autism Spectrum Disorder Research
- RNA modifications and cancer
- Alzheimer's disease research and treatments
- Hearing, Cochlea, Tinnitus, Genetics
- Sleep and Wakefulness Research
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- Transcranial Magnetic Stimulation Studies
- Biomedical Ethics and Regulation
- Retinal Development and Disorders
Juntendo University
2016-2025
Keio University Hospital
2012-2021
Keio University
2010-2020
Indiana University School of Medicine
2018
Czech Academy of Sciences, Institute of Physiology
2015
University of Toronto
2006-2009
Tohoku University
2005
Dokkyo University
2005
Japan Science and Technology Agency
2001-2005
Osaka University
1999-2001
Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance. Mutations presenilin 1 (PS1) 2 (PS2) are causative factors for autosomal-dominant early-onset familial AD (FAD). Induced pluripotent stem cell (iPSC) technology can be used to model human disorders provide novel opportunities study cellular mechanisms establish therapeutic strategies against various diseases, including neurodegenerative diseases. Here...
Abstract Background Parkinson’s disease (PD) is a neurodegenerative characterized by selective degeneration of dopaminergic neurons in the substantia nigra (SN). The familial form PD, PARK2, caused mutations parkin gene. -knockout mouse models show some abnormalities, but they do not fully recapitulate pathophysiology human PARK2. Results Here, we generated induced pluripotent stem cells (iPSCs) from two PARK2 patients. iPSC-derived showed increased oxidative stress and enhanced activity...
Hu proteins are mammalian embryonic lethal abnormal visual system (ELAV)-like neuronal RNA-binding that contain three RNA recognition motifs. Although Drosophila ELAV is required for the correct differentiation and survival of neurons, roles played by genes in nervous remain largely unknown. To explore vivo functions mouse proteins, we overexpressed them rat pheochromocytoma PC12 cells, where they induced phenotype absence nerve growth factor. We have characterized various forms mHuB mHuC...
Neural Hu proteins (HuB/C/D) are RNA-binding that have been shown to induce neuronal differentiation activity when overexpressed in immature neural progenitor cells or undifferentiated tumors. Newly generated HuD- deficient mice exhibited a transient impaired-cranial-nerve-development phenotype at an early embryonic stage. Adult HuD -deficient abnormal hind-limb reflex and poor rotarod performance. Analysis of neurosphere formation revealed the number self-renewal capacity stem/progenitor...
Abstract Background Dravet syndrome is a devastating infantile-onset epilepsy with cognitive deficits and autistic traits caused by genetic alterations in SCN1A gene encoding the α-subunit of voltage-gated sodium channel Na v 1.1. Disease modeling using patient-derived induced pluripotent stem cells (iPSCs) can be powerful tool to reproduce this syndrome’s human pathology. However, no such effort has been reported date. We here report cellular model for DS that utilizes iPSCs. Results...
The accumulation of misfolded proteins is a common pathological feature many neurodegenerative disorders, including synucleinopathies such as Parkinson9s disease (PD), which characterized by the presence α-synuclein (α-syn)-containing Lewy bodies. However, although recent studies have investigated α-syn and propagation in neurons, molecular mechanisms underlying transmission been largely unexplored. Here, we examined monogenic form synucleinopathy caused loss-of-function mutations lysosomal...
Significance Parkinson’s disease (PD) is a chronic and progressive movement disorder; however, the precise mechanisms of its etiology remain largely unknown. Soluble epoxide hydrolase (sEH) plays key role in inflammation associated with PD pathogenesis. The sEH inhibitor or deletion gene protected against MPTP-induced neurotoxicity mouse brain. Furthermore, expression protein (or mRNA) was higher striatum MPTP-treated mice, patients dementia Lewy bodies (DLB), neurons from iPSCs patient...
Pelizaeus-Merzbacher disease (PMD) is a form of X-linked leukodystrophy caused by mutations in the proteolipid protein 1 (PLP1) gene. Although PLP1 proteins with missense have been shown to accumulate rough endoplasmic reticulum (ER) model animals and cell lines transfected mutant genes, exact pathogenetic mechanism PMD has not previously clarified. In this study, we established induced pluripotent stem cells (iPSCs) from two patients carrying mutation differentiated them into...
Retinitis pigmentosa (RP) is an inherited human retinal disorder that causes progressive photoreceptor cell loss, leading to severe vision impairment or blindness. However, no effective therapy has been established date. Although genetic mutations have identified, the available clinical data are not always sufficient elucidate roles of these in disease pathogenesis, a situation partially due differences backgrounds. We generated induced pluripotent stem cells (iPSCs) from RP patient carrying...
Abstract Given the complexity and heterogeneity of genomic architecture underlying schizophrenia, molecular analyses these patients with defined large effect-size defects could provide valuable clues. We established human-induced pluripotent stem cells from two schizophrenia 22q11.2 deletion (two cell lines each subject, total four lines) three controls (total lines). Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration neurogenic-to-gliogenic competence...
Abstract Recently, the genetic variability in lysosomal storage disorders has been implicated pathogenesis of Parkinson’s disease. Here, we found that variants prosaposin (PSAP), a rare causative gene various types disorders, are linked to Genetic mutation screening revealed three pathogenic mutations saposin D domain PSAP from families with autosomal dominant Whole-exome sequencing no other previously identified disease-causing or disorder-causing genes. A case-control association study two...
The pathologic hallmark of Parkinson's disease is the accumulation α-synuclein-containing Lewy bodies/neurites almost exclusively in neurons, and rarely glial cells. However, emerging evidence suggests that glia such as astrocytes play an important role development α-synuclein pathology. Using induced pluripotent stem-derived dopaminergic neurons from healthy subjects patients carrying mutations lysosomal ATP13A2 , a monogenic form synucleinopathy, we found rapidly internalized α-synuclein,...
Parkinson's disease is characterized by the presence of α-synuclein (α-syn) primarily containing Lewy bodies in neurons. Despite decades extensive research on α-syn accumulation, its molecular mechanisms have remained largely unexplored. Recent studies us and others suggested that extracellular vesicles (EVs), especially exosomes, can mediate release from cells, inhibiting this pathway could result increased intracellular levels. In study, we discovered elevated levels themselves lead to...
Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results pigment disorders. Additionally, melanomas are considered to arise mutations that accumulate melanocyte stem cells. The mechanisms underlying differentiation defining characteristics of cells humans are, however, largely unknown. In present study, we set out generate human iPS vitro, leading a preliminary investigation differentiation. We generated cell lines dermal...
Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation of pluripotent (iPSCs). These NSCs gave rise to both neurons glial even at early passages, while derived embryonic (ESCs)/iPSCs differentiated mainly into neurons. Epidermal growth factor-dependent neurosphere cultivation efficiently propagated these gliogenic eliminated residual that could form teratomas in vivo. We concluded...
Rett syndrome (RTT) is one of the most prevalent neurodevelopmental disorders in females, caused by de novo mutations X-linked methyl CpG-binding protein 2 gene, MECP2. Although abnormal regulation neuronal genes due to mutant MeCP2 thought induce autistic behavior and impaired development RTT patients, precise cellular mechanisms underlying aberrant neural progression remain unclear.Two sets isogenic pairs either wild-type or MECP2-expressing human induced pluripotent stem cell (hiPSC)...
The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of subtype specificity disease phenotypes remains elusive. Although in vitro models employing human pluripotent stem cells (PSCs) have great potential to clarify association subtypes with disease, it is currently difficult compare various PSC-derived This due limited number whose induction established, different cultivation protocols for each subtype. Here, we...
Highlights•Modeling familial ALS (FALS) using iPSC-derived motor neurons•Aberrant gene expression and/or splicing in FALS neuron precursor cells•Mis-localization of mutant FUS protein neurons•Increased apoptosis neuronsSummaryAmyotrophic lateral sclerosis (ALS) is a late-onset disorder. Although its neuropathology well understood, the cellular and molecular mechanisms are yet to be elucidated due limitations currently available human genetic data. In this study, we generated induced...
Induced pluripotent stem cell (iPSC) technology can be used to model human disorders, create cell-based models of diseases, including neurodegenerative and in establishing therapeutic strategies. To detect subtle cellular abnormalities associated with common late-onset disease iPSCs, valid control iPSCs derived from healthy donors free serious diseases are necessary. Here, we report the generation fibroblasts obtained immediately postmortem centenarian (106- 109-years-old) who were extremely...
Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, frequent syndromic form hereditary hearing loss, is associated with mutations in anion exchanger pendrin. Loss pendrin function as an thought be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant aggregates increased susceptibility cellular stresses cochlear epithelial cells...
The proper functions of cortical circuits are dependent upon both appropriate neuronal subtype specification and their maturation to receive signaling. These events establish a balanced circuit that is important for learning, memory, emotion, complex motor behaviors. Recent research points mRNA metabolism as key regulator this development process. Hu antigen D (HuD), an RNA-binding protein, has been implicated in the establishment identity neurite outgrowth vitro . Therefore, we investigated...