A5003580639- RNA Research and Splicing
- Retinal Development and Disorders
- RNA modifications and cancer
- MicroRNA in disease regulation
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Diseases and Treatments
- Photochromic and Fluorescence Chemistry
- RNA regulation and disease
- Circular RNAs in diseases
- Hedgehog Signaling Pathway Studies
- FOXO transcription factor regulation
- Retinoids in leukemia and cellular processes
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Mechanisms of cancer metastasis
- Cellular transport and secretion
- RNA Interference and Gene Delivery
- Retinal and Macular Surgery
- Corneal Surgery and Treatments
- Glaucoma and retinal disorders
- Photoreceptor and optogenetics research
- Epigenetics and DNA Methylation
The University of Tokyo
2011-2020
Tokyo University of Science
2006-2017
Agency for Science, Technology and Research
2012-2015
Institute of Molecular and Cell Biology
2012-2015
Wellcome Sanger Institute
2014
Houston Methodist
2014
Zero to Three
2012
Purpose.: The authors sought to identify cell surface markers of photoreceptor and its precursor cells. Methods.: expression CD antigens that label both temporally spatially distinct populations mouse retinal cells were examined. Of the antibodies showed positive signals in cells, CD73 was focused on for more detailed analyses. Results.: Mouse subpopulations expressed first appeared around birth subsequently increased dramatically number, eventually representing than 90% adult. CD73+...
Neural stem cells (NSCs) are considered to be the cell of origin glioblastoma multiforme (GBM). However, genetic alterations that transform NSCs into glioma-initiating remain elusive. Using a unique transposon mutagenesis strategy mutagenizes in culture, followed by additional rounds generate tumors vivo, we have identified genes and signaling pathways can cells. Mobilization Sleeping Beauty transposons induced immortalization astroglial-like cells, which were then able with characteristics...
Abstract Medulloblastoma is the most common pediatric brain tumor, and in ∼25% of cases, it driven by aberrant activation Sonic Hedgehog (SHH) pathway granule neuron precursor (GNP) cells. In this study, we identified novel medulloblastoma driver genes through a transposon mutagenesis screen developing wild-type Trp53 mutant mice. Twenty-six candidates were along with established such as Gli1 Crebbp. The transcription factor FoxR2, frequent gene screen, overexpressed small subset human SHH...
Transposon-based insertional mutagenesis is a valuable method for conducting unbiased forward genetic screens to identify cancer genes in mice. We used this system elucidate factors involved the malignant transformation of neural stem cells into glioma-initiating cells. identified an RNA-binding protein, La-related protein 4b (LARP4B), as candidate tumor-suppressor gene glioma. LARP4B expression was consistently decreased human glioma and cell lines compared with normal Moreover,...
Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte‐derived macrophages into CNS, resulting in coexistence these two populations within same lesion, though their distinct features remain elusive. To investigate impact rod photoreceptor degeneration on activation, we generated a toxin‐mediated genetic model degeneration. Rod injury induced proliferation migration toward photoreceptors. Bone marrow transplantation revealed invasion retina, with...
Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived can cause retinal inflammation which accelerates photoreceptor cell death, details of how these cells are activated during degeneration (RD) remain uncertain. Therefore, it is important to clarify play a dominant role fueling inflammation. However, distinguishing between microglia difficult using conventional techniques such as markers (e.g., Iba-1). Recently, two mouse models...
Using quantitative PCR-based miRNA arrays, we comprehensively analyzed the expression profiles of miRNAs in human and mouse embryonic stem (ES), induced pluripotent (iPS), somatic cells. Immature cells were purified using SSEA-1 or SSEA-4 used for profiling. Hierarchical clustering consensus by nonnegative matrix factorization showed two major clusters, ES/iPS other cell groups, as previously reported. Principal components analysis (PCA) to identify that segregate these groups identified...
Glioblastoma is the most common form of malignant brain cancer and has a poor prognosis in adults. We identified Dhx15 as candidate tumour suppressor gene glioma by transposon-based mutagenesis. an adenosine triphosphate (ATP)-dependent RNA helicase belonging to DEAH-box (DHX) family, but its role remains elusive. DHX15 expression levels were examined cell lines. functions gain- loss-of-function analyses. Protein motifs required for function investigated analysis mutant proteins. was lower...
Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify glia-specific molecular signatures during development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purified EGFP-positive other EGFP-negative cells developing retinas subjected them RNA sequencing analysis. Gene expression pattern cell was similar genes expressed in progenitors, they were downregulated lineages. Then,...
Abstract Background Embryonal tumors in the central nervous system (CNS) are primary, aggressive, and poorly differentiated pediatric brain tumors. We identified forkhead box R2 (Foxr2) as an oncogene for medulloblastoma through a transposon-based insertional mutagenesis screen. Foxr2 translocation has been subset of human embryonal CNS, designated CNS neuroblastoma with activation (CNS NB-Foxr2); however, vivo functions remain elusive. Methods analyzed effect overexpression mouse by...
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammation and angiogenesis. In this study, we investigated the possible involvement of S1P in pathology light-induced retinal degeneration vivo vitro. The intracellular sphingosine kinase (SphK) activity photoreceptor cell line (661W cells) was significantly increased by exposure to light. enhancement SphK1 expression dependent on illumination, all-trans-retinal promoted expression. treatment reduced protein B (Akt)...
Glioma is the most common form of malignant brain cancer in adults. The Sleeping Beauty ( SB ) transposon‐based glioma mouse model allows for effective vivo analysis candidate genes. In present study, we developed a transposon vector that encodes triple combination platelet‐derived growth factor subunit A PDGFA ), and sh RNA s against Nf1 Trp53 (shNf1/shp53). Initiation progression were monitored by expression fluorescent protein. Transduction into neural progenitor stem cells NPC...
Abstract The RNA‐binding protein Musashi1 (Msi1) is one of two mammalian homologues Drosophila Musashi , which required for the asymmetric cell division sensory organ precursor cells. In mouse central nervous system (CNS), Msi1 preferentially expressed in mitotically active progenitor cells ventricular zone (VZ) neural tube during embryonic development and subventricular (SVZ) postnatal brain. Previous studies showed that SVZ can contribute to long‐term neurogenesis olfactory bulb (OB), but...
Purpose: Forkhead box protein P1 (Foxp1) is a transcriptional repressor expressed in many tissues. We identified Foxp1 as highly gene retinal progenitor cells and investigated its roles during eye development. Methods: Mouse eyes with gain- or loss-of-function were established vitro vivo. Results: overexpression resulted reduced rod increased cone photoreceptors. However, retina-specific knockout of was not associated differentiation abnormalities. the lens early development, continued to be...
Purpose: The role of activated retinal microglia in driving degeneration has been implicated a number vivo disease models. Here, we investigated the primary consequences microglial activation by specific expression constitutively active Ras transgenic mouse model before onset any degenerative changes retina. Methods: double lines CAG-LSL-RasV12-IRES-EGFP; Cx3cr1CreER/+ (Cx3cr1-RasV12 mice) and CAG-LSL-EGFP; Cx3cr1CreER_+ (control were generated. RasV12 was induced tamoxifen administration,...
Abstract Ciliary epithelium (CE), which consists of nonpigmented and pigmented layers, develops from the optic vesicle. However, molecular mechanisms underlying CE development have not been closely examined, in part because cell-surface markers suitable for specific labeling subregions retina were unknown. Here, we identified CD138/syndecan-1 stage embryonic antigen-1 (SSEA-1) CD15 as antigens marking CE, respectively. During retinal development, both CD138 SSEA-1 expressed early stage,...