A5020820886- Zebrafish Biomedical Research Applications
- Angiogenesis and VEGF in Cancer
- Down syndrome and intellectual disability research
- Retinal Development and Disorders
- Congenital heart defects research
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
- Chromatin Remodeling and Cancer
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Viral Infectious Diseases and Gene Expression in Insects
- Aortic aneurysm repair treatments
- Systemic Lupus Erythematosus Research
- Click Chemistry and Applications
- Electrospun Nanofibers in Biomedical Applications
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Infectious Aortic and Vascular Conditions
- Mesenchymal stem cell research
- Signaling Pathways in Disease
- Pancreatic function and diabetes
- Genomics and Rare Diseases
Nara Medical University
2020-2024
Indiana University School of Medicine
2017-2024
Indiana University – Purdue University Indianapolis
2017-2024
Osaka University
2016-2021
Nara Medical University Hospital
2020
Indiana University
2020
Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic GATA1. To better understand functional interplay between trisomy 21 GATA1 hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs)...
Most circulating endothelial cells are apoptotic, but rare colony-forming (C-ECFCs), also known as blood outgrowth cells, with proliferative and vasculogenic activity can be cultured; however, the origin naive function of these C-ECFCs remains obscure. Herein, detailed lineage tracing revealed murine emerged in early postnatal period, displayed high potential enriched frequency clonal compared tissue-resident ECFCs, were not committed to or derived from BM hematopoietic system ECFCs. In...
Abstract Astrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in fate-specification step has been reported, mechanisms and key regulators underlying accelerated proliferation astrocyte precursor cells (APCs) DS remain elusive. Here, we established human isogenic cell line panel based DS-specific induced pluripotent stem cells, XIST -mediated transcriptional silencing system trisomic chromosome 21,...
Significance Statement Extreme stress, such as life-threatening sepsis, triggers the integrated stress response and causes translation shutdown, a hallmark of late-phase, sepsis-induced kidney injury. Although brief period shutdown could be cytoprotective, prolonged repression can have negative consequences has been shown to contribute failure. Using murine model endotoxemia, authors show that duration stress-induced in shortened by overexpressing protein phosphatase 1 regulatory subunit 15A...
Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature have less regenerative potential. However, it is unclear whether vascular endothelial (ECs) also replenished with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative...
Human induced pluripotent stem cells (hiPSCs) were differentiated into a specific mesoderm subset characterized by KDR + CD56 APLNR (KNA ) expression. KNA had high clonal proliferative potential and specification endothelial colony-forming cell (ECFCs) phenotype. perfused blood vessels when implanted subcutaneously the flank of nonobese diabetic/severe combined immunodeficient mice injected vitreous type 2 diabetic ( db/db mice). Transcriptomic analysis showed that differentiation hiPSCs...
Chromosome abnormalities induces profound alterations in gene expression, leading to various disease phenotypes. Recent studies on yeast and mammalian cells have demonstrated that aneuploidy exerts detrimental effects organismal growth development, regardless of the karyotype, suggesting aneuploidy-associated stress plays an important role pathogenesis. However, whether how this effect alters cellular homeostasis long-term features human are not fully understood. Here, we aimed investigate...
Abstract Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence supernumerary chromosome 21 in Down syndrome may perturb nuclear architecture at different levels, which normally optimised to maintain physiological balance expression. However, it has not been clearly elucidated whether how aberrant configuration affects activities. To...
Abstract Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that gain a exerts an adverse impact cell physiology, regardless karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common human fibroblasts trisomy 18, 13, whether how this aneuploidy-associated stress acts other lineages...
Abstract Infantile liver failure syndrome type 1 (ILFS1) is a recently recognized autosomal recessive disorder caused by deleterious mutations in the leucyl‐tRNA synthetase gene ( LARS1 ). The enzyme responsible for incorporation of amino acid leucine during protein polypeptide synthesis. Individuals with typically show from infancy to early childhood periods illness or other physiological stress. While 25 patients 15 families ILFS1 have been reported literature, histological reports autopsy...
Objective Endothelial dysfunction is central to the pathogenesis of many rheumatic diseases, typified by vascular inflammation and damage. Immunosuppressive drugs induce disease remission lead improved patient survival. However, there remains a higher incidence cardiovascular in these patients even after adequate control. The purpose this study was determine effect mycophenolic acid (MPA), commonly used immunosuppressive drug rheumatology, on blood vessel or circulating endothelial colony...
Abstract Cell therapy using endothelial cells (ECs) has great potential for the treatment of congenital disorders, such as hemophilia A. sheet technology utilizing a thermoresponsive culture dish is promising approach to efficiently transplant donor cells. In this study, new method prepare terminus‐selective heparin‐immobilized surfaces developed facilitate preparation EC sheets. Alkynes are introduced reducing terminus heparin via reductive amination. Cu‐catalyzed azide‐alkyne cycloaddition...
Abstract The eIF2 initiation complex is central to maintaining a functional translation machinery. Extreme stress such as life-threatening sepsis exposes vulnerabilities in this tightly regulated system, resulting an imbalance between the opposing actions of kinases and phosphatases on main regulatory subunit eIF2α. Here, we report that shutdown hallmark established sepsis-induced kidney injury brought about by excessive eIF2α phosphorylation sustained blunted expression counterregulatory...
first_page settings Order Article Reprints Font Type: Arial Georgia Verdana Size: Aa Line Spacing: Column Width: Background: Open AccessAbstract Human Pluripotent Stem Cells from Diabetic and Nondiabetics Improve Retinal Pathology in Mice † by Chang-Hyun Gil 1,2, Dibyendu Chakraborty 3, Cristiano P. Vieira Nutan Prasain 1,4, Sergio Li Calzi Seth D. Fortmann 3,5, Ping Hu Kimihiko Banno 1,6, Mohamed Jamal 7,8, Chao Huang Micheli S. Sielski Yang Lin 1,9, Xinxin 10,11, Mariana Dupont Jason...
Human induced pluripotent stem cells (hiPSC) differentiated into a specific mesoderm subset expressing vascular endothelial growth factor receptor 2, neural cell adhesion molecule 1, and apelin G protein-coupled APJ (called KNA+), possessed all of the phenotypic functional colony forming potential that resides in differentiating hiPSC. Thus, we postulated KNA+ treatment would correct diabetic retinal capillary vasodegeneration. derived from (D) non-diabetic (N) patient-derived hiPSC...
Abstract Astrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in fate-specification step has been reported, mechanisms and key regulators underlying accelerated proliferation astrocyte precursor cells (APCs) DS remain elusive. Here, we established an isogenic cell line panel, based DS-specific induced pluripotent stem cells, XIST -mediated transcriptional silencing system trisomic chromosome 21,...
Summary Most circulating endothelial cells are apoptotic, but rare colony forming (C-ECFCs) with proliferative and vasculogenic activity can be cultured; the origin naïve function of these C-ECFCs remains obscure. Herein, detailed lineage tracing reveals murine emerge in early postnatal period, display high potential, enriched frequency clonal compared to tissue-resident ECFCs, not committed or derived from bone marrow hematopoietic system ECFCs. In human subjects, present CD34 bright cord...