A5038145868- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Medical Imaging Techniques and Applications
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Genomics and Phylogenetic Studies
- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Virus-based gene therapy research
- Lymphatic System and Diseases
- Retinal Development and Disorders
- Protein Structure and Dynamics
- Immunotherapy and Immune Responses
- Metabolomics and Mass Spectrometry Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Trypanosoma species research and implications
- Advanced biosensing and bioanalysis techniques
- Molecular Biology Techniques and Applications
- Protein Degradation and Inhibitors
RIKEN Center for Integrative Medical Sciences
2011-2023
Hiroshima University
2020-2023
Age UK
2022
George Washington University
2005
Center for Infectious Disease Research
2005
University of Washington
2005
Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that diploid genome contains a predicted 22,570 proteins encoded by genes, which 12,570 represent allelic pairs. Over 50% consists repeated sequences, such as retrotransposons and genes for large families surface molecules, include trans-sialidases, mucins, gp63s, novel family (>1300 copies) mucin-associated protein (MASP) genes. Analyses T. cruzi, brucei , Leishmania major (Tritryp) genomes imply differences...
Abstract Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes 1,2 . Previous metagenomic studies have described characteristics of gut microbiota their roles in metabolizing major nutrients insulin 3–9 In particular, carbohydrate metabolism commensals has been proposed to contribute up 10% host’s overall energy extraction 10 , thereby playing a role pathogenesis obesity prediabetes 3,4,6 Nevertheless, mechanism remains unclear. Here we...
Abstract Mammalian genomes encode tens of thousands noncoding RNAs. Most transcripts exhibit nuclear localization and several have been shown to play a role in the regulation gene expression chromatin remodeling. To investigate function such RNAs, methods massively map genomic interacting sites multiple developed; however, these some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated sequenced (RADICL-seq), technology that maps genome-wide RNA–chromatin interactions...
The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based profiling on extended dense time course response monocyte-derived macrophages grown macrophage colony-stimulating factor (CSF1) bacterial lipopolysaccharide (LPS). We propose that this system provides a model for differentiation adaptation monocytes entering intestinal lamina...
Abstract Single-cell transcriptomic profiling is a powerful tool to explore cellular heterogeneity. However, most of these methods focus on the 3′-end polyadenylated transcripts and provide only partial view transcriptome. We introduce C1 CAGE, method for detection transcript 5′-ends with an original sample multiplexing strategy in TM microfluidic system. first quantifiy performance CAGE find it as accurate sensitive other then use profile promoter enhancer activities response TGF-β lung...
Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as inputs one target gene in the region. The genes often transcription factors involved embryonic development and differentiation. GRBs contain extensive deserts, well additional 'bystander' intertwined with HCNEs but whose expression function unrelated to those gene. tight regulation genes, complex arrangement inputs, differential responsiveness region call...
Mechanistic insights into the molecular events by which exercise enhances skeletal muscle phenotype are lacking, particularly in context of type 2 diabetes. Here, we unravel a fundamental role for exercise-responsive cytokines (exerkines) on development and growth individuals with normal glucose tolerance or Acute triggered an inflammatory response muscle, concomitant infiltration immune cells. These effects were potentiated In to contraction hypoxia, mainly produced endothelial cells...
The application of isothermal amplification technologies is rapidly expanding and currently covers different areas such as infectious disease, genetic disorder drug dosage adjustment. Meanwhile, many have complex reaction processes often require a fine-tuned primer set where existing design tools are not sufficient. We developed selection system for one important primer, the turn-back (TP), which commonly used in loop-mediated (LAMP) smart process (SmartAmp). chose 78 parameters related to...
Immediate early genes are considered to play important roles in dynamic gene regulatory networks following exposure appropriate stimuli. One of the immediate genes, growth response 1 (EGR-1), has been implicated differentiation human monoblastoma cells along monocytic commitment treatment with phorbol ester. EGR-1 thought work as a modifier monopoiesis, but precise function not fully elucidated.We performed first genome-wide analysis binding sites by chromatin immunoprecipitation promoter...
The immediate-early response mediates cell fate in to a variety of extracellular stimuli and is dysregulated many cancers. However, the specificity across types, roles non-coding RNAs are not well understood. Using large collection densely-sampled time series expression data we have examined induction unparalleled detail, types stimuli. We exploit cap analysis gene (CAGE) datasets directly measure promoter activities over time. novel method for identify transcripts with patterns that closely...
VEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of progenitor cells from embryonic veins and maintaining expression PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene is still not completely understood. We used cap analysis (CAGE) RNA sequencing to characterize transcriptional changes invoked by VEGF-C LECs identify transcription factors (TFs) involved. found that MAFB, TF involved...
Abstract Owing to safety concerns or insufficient efficacy, few drug candidates are approved for marketing. Drugs already on the market may be withdrawn due adverse effects (AEs) discovered after introduction. Comprehensively investigating on-/off-target of drugs can help expose AEs during development process. We have developed an integrative framework systematic identification pathways and elucidation underlying regulatory mechanisms, by combining promoter expression profiling treatment...
Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes molecular pathways. While skeletal muscle baseline differences between exercise-trained untrained individuals have been previously investigated, it remains unclear how history influences human multi-omics responses acute exercise. We recruited extensively characterized 24 categorized as endurance athletes with >15 years of history, strength or control subjects....
The pathway for RNA interference is widespread in metazoans and participates numerous cellular tasks, from gene silencing to chromatin remodeling protection against retrotransposition. unicellular eukaryote Trypanosoma cruzi missing the canonical RNAi unable induce RNAi-related processes. To further understand alternative pathways operating this organism, we have performed deep sequencing genome-wide analyses of a size-fractioned cDNA library (16–61 nt) epimastigote life stage. Deep...
Abstract Background Histone modifications play an important role in gene regulation. Acetylation of histone 3 lysine 9 (H3K9ac) is generally associated with transcription initiation and unfolded chromatin, thereby positively influencing expression. Deep sequencing the 5' ends transcripts using DeepCAGE delivers detailed information about architecture expression level promoters. The combination H3K9ac ChIP-chip a myeloid leukemia cell line (THP-1) allowed us to study spatial distribution...
Abstract MicroRNAs (miRNA) modulate gene expression through feed-back and forward loops. Previous studies identified miRNAs that regulate transcription factors, including Peroxisome Proliferator Activated Receptor Gamma (PPARG), in adipocytes, but whether they influence adipogenesis via such regulatory loops remain elusive. Here we predicted validated a novel feed-forward loop regulating involved miR-27a/b-3p, PPARG Secretory Carrier Membrane Protein 3 (SCAMP3). In this loop, of both SCAMP3...
Controlling cell fate has great potential for regenerative medicine, drug discovery, and basic research. Although transcription factors are able to promote reprogramming transdifferentiation, methods based on their upregulation often show low efficiency. Small molecules that can facilitate conversion between types ameliorate this problem working through safe, rapid, reversible mechanisms. Here, we present DECCODE, an unbiased computational method identification of such transcriptional data....
ABSTRACT Lymphangiogenesis plays a crucial role during development, in cancer metastasis and inflammation. Activation of VEGFR-3 (also known as FLT4) by VEGF-C is one the main drivers lymphangiogenesis, but transcriptional events downstream activation are largely unknown. Recently, we identified wave immediate early transcription factors that upregulated human lymphatic endothelial cells (LECs) within first 30 to 80 min after activation. Expression these must be regulated additional...
Drug treatment induces cell type specific transcriptional programs, and as the number of combinations drugs types grows, cost for exhaustive screens measuring drug response becomes intractable. We developed DeepCellState, a deep learning autoencoder-based framework, predicting induced state in after treatment, based on another type. Training method large collection perturbation profiles, prediction accuracy improves significantly over baseline alternative approaches when applying to two...
Abstract Polycomb group proteins (PcG), polycomb repressive complexes 1 and 2 (PRC1 2), repress lineage inappropriate genes during development to maintain proper cellular identities. It has been recognized that PRC1 localizes at the replication fork, however, precise functions of DNA are elusive. Here, we reveal a variant containing PCGF1 (PCGF1-PRC1) prevents overloading activators chromatin remodeling factors on nascent thereby mediates deposition nucleosomes correct downstream...
The promoters of immediate early genes (IEGs) are rapidly activated in response to an external stimulus. These genes, also known as primary have been identified a range cell types, under diverse extracellular signals and using varying experimental protocols. Whereas genomic dissection on case-by-case basis has not resulted comprehensive catalogue IEGs, rigorous meta-analysis eight genome-wide FANTOM5 CAGE (cap analysis gene expression) time course datasets reveals successive waves promoter...
Abstract Mammalian genomes encode tens of thousands noncoding RNAs. Most transcripts exhibit nuclear localization and several have been shown to play a role in the regulation gene expression chromatin remodelling. To investigate function such RNAs, methods massively map genomic interacting sites multiple developed. However, they still present some limitations. Here, we introduce R NA A nd D Interacting C omplexes L igated seq uenced (RADICL-seq), technology that maps genome-wide...
Regenerative medicine relies on basic research outcomes that are only practical when cost effective. The human eyeball requires the retinal pigment epithelium (RPE) to interface neural retina and choroid at large. Millions of people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among RPE degradation pathologies. Recently, autologous pluripotent stem-cell-derived cells were prohibitively expensive due time; therefore, we developed faster...