A5073600658- Neural dynamics and brain function
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- stochastic dynamics and bifurcation
- Neural Networks and Applications
- Neuroscience and Neural Engineering
- Nonlinear Dynamics and Pattern Formation
- Advanced Memory and Neural Computing
- Gene Regulatory Network Analysis
- Corneal surgery and disorders
- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- EEG and Brain-Computer Interfaces
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Photoreceptor and optogenetics research
- Chromatin Remodeling and Cancer
- Biomedical Ethics and Regulation
- Corneal Surgery and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Glutathione Transferases and Polymorphisms
- Nuclear Receptors and Signaling
Osaka University
2025
Foundation for Biomedical Research and Innovation
2022-2025
Kyoto University
2009-2024
Hiroshima City University
2020
Japan Science and Technology Agency
2000-2016
RIKEN Center for Integrative Medical Sciences
2013
Kyoto College of Graduate Studies for Informatics
2007
Abstract Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies Parkinson’s disease (PD). The regulatory criteria the clinical application of these therapies, however, have not been established. Here we show results our pre-clinical study, in which evaluate safety and efficacy progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm characteristics DAPs by vitro analyses. also verify that DAP population...
Immune attacks are key issues for cell transplantation. To assess the safety and immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored rejections by routine ocular examinations as well lymphocytes-graft reaction...
A first-in-human investigator-initiated clinical study of a corneal endothelial cell substitute (CLS001) derived from clinical-grade induced pluripotent stem (iPSC) line shows improvement visual acuity and stromal edema, with no adverse events for up to 1 year after surgery the treatment bullous keratopathy. While preclinical tests, including multiple whole-genome analysis tumorigenicity tests adhering Food Drug Administration (FDA) draft guidelines, are negative, an additional conducted on...
In order to expand the promise of regenerative medicine using allogeneic induced pluripotent stem cells (iPSCs), precise and efficient genome editing human leukocyte antigen (HLA) genes would be advantageous minimize immune rejection caused by mismatches HLA type. However, clinical-grade multiple in iPSC lines remains unexplored. Here, we optimized protocol for good manufacturing practice (GMP)-compatible CRISPR-Cas9 deplete three gene locus (HLA-A, HLA-B, CIITA genes) simultaneously...
SummaryBackgroundThe loss of corneal epithelial stem cells from the limbus at edge cornea has severe consequences for vision, with pathological manifestations a limbal stem-cell deficiency (LSCD) difficult to treat. Here, best our knowledge, we report world's first use cell sheets derived human induced pluripotent (iPSCs) treat LSCD.MethodsThis non-randomised, single-arm, clinical study involved four eyes patients LSCD Department Ophthalmology, Osaka University Hospital. They comprised woman...
Abstract Background Cell- or tissue-based regenerative therapy is an attractive approach to treat heart failure. A tissue patch that can safely and effectively repair damaged muscle would greatly improve outcomes for patients with In this study, we conducted a preclinical proof-of-concept analysis of the efficacy safety clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches. Methods hiPSC line was established using peripheral blood mononuclear cells from...
Inhibitory interneurons target precise membrane regions on pyramidal cells, but differences in their functional effects somata, dendrites and spines remain unclear. We analyzed inhibitory synaptic events induced by cortical, fast-spiking (FS) basket cells which innervate dendritic shafts as well cell somata. Serial electron micrograph (EMg) reconstructions showed that somatic synapses were larger than contacts. Simulations with anatomical physiological data reveal between different...
Dendritic trees influence synaptic integration and neuronal excitability, yet appear to develop in rather arbitrary patterns. Using electron microscopy serial reconstructions, we analyzed the dendritic of four morphologically distinct neocortical interneuron subtypes reveal two underlying organizational principles common all. First, cross-sectional areas at any given point within a dendrite were proportional summed length all segments distal that point. Consistent with this observation,...
Abstract ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes: canonical BAF (cBAF), polybromo (PBAF), and a newly described non-canonical (ncBAF). While cBAF PBAF regulate fates of multiple cell types, roles for ncBAF hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery disrupted expression BRD9, an essential component ncBAF, cancers, including clonal disorders, we evaluate here the role BRD9 normal malignant HSCs. loss...
Fast-spiking (FS) interneurons have specific types (Kv3.1/3.2 type) of the delayed potassium channel, which differ from conventional Hodgkin-Huxley (HH) type channel (Kv1.3 in several aspects. In this study, we show dramatic effects Kv3.1/3.2 on synchronization FS interneurons. We analytically that two identical electrically coupled modeled with fire synchronously at arbitrary firing frequencies, unlike similarly neurons Kv1.3 frequency-dependent synchronous and antisynchronous states....
Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing accumulation genetic abnormalities. Therefore, tests predict formation after transplantation. Here, we administered iPSC with or without single-nucleotide variants (SNVs) and deletions cancer-related genes various genomic copy number variant (CNV) profiles into immunodeficient mice...
The hierarchical organization of hematopoietic stem cells (HSCs) governing adult hematopoiesis has been extensively investigated. However, the dynamic epigenomic transition from fetal to remains incompletely understood, particularly regarding involvement epigenetic factors. In this study, we investigate roles BRD9, an essential component non-canonical BAF (ncBAF) complex known govern fate HSCs, in hematopoiesis. Consistent with observations hematopoiesis, BRD9 loss impairs HSC stemness and...
We demonstrate that the phase response curve (PRC) can be reconstructed using a weighted spike-triggered average of an injected fluctuating input. The key idea is to choose weight proportional magnitude fluctuation oscillatory period. Particularly, when neuron exhibits random switching behavior between two bursting modes, corresponding PRCs simultaneously reconstructed, even from data single trial. This method offers efficient alternative experimental investigation systems, without need for...
Highlights•ESRG (+) early reprogramming cells do not proliferate due to RB activation•MYC does facilitate appearance of ESRG but induces their proliferation•MYC inactivates by suppressing p16 and p21, with the latter mediated through LIN41•Immortalized show efficient without exogenous MYCSummaryHere, we report that MYC rescues human undergoing from a proliferation pause induced OCT3/4, SOX2, KLF4 (OSK). We identified as marker is expressed day 3 after OSK induction. On 4, positive converted...
Detailed genomic and epigenomic analyses of MECOM (the MDS1 EVI1 complex locus) have revealed that inversion or translocation chromosome 3 drives inv(3)/t(3;3) myeloid leukemias via structural rearrangement an enhancer upregulates transcription EVI1. Here, we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform is frequently present in acute leukemia (AML) directly contributes to leukemic transformation. This generated by mutations the core RNA splicing factor...
Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, LMYC, in human somatic cells improves quality of reprogramming pluripotency. H1FOO-DD expression was associated altered chromatin accessibility around pluripotency genes suppression innate immune response. Notably, generates induced lower...
Abstract Mesenchymal stem cells (MSCs) can show trisomy 7; however, the safety of these has not been fully investigated. The purposes this study were to determine ratio patients whose synovial MSCs transplanted clinically, intensively investigate with 7 from a perspective, and follow up for 5 years after transplantation. Synovial at passage 0 into knee degenerative meniscus tears in 10 patients, checked years. evaluated passages 15 by G-bands digital karyotyping, was found 3 patients. In...
Abstract High-affinity memory B cells are preferentially selected during secondary responses and rapidly differentiate into antibody-producing cells. However, it remains unknown whether only high-affinity, mutated simply expand to dominate the response or if in fact with a diverse VH repertoire, including those no mutations, accumulate somatic mutations create new repertoire through process of affinity maturation. In this report, we took approach address question by analyzing gene IgG1+...