A5025271675- Renal and related cancers
- Pluripotent Stem Cells Research
- Renal cell carcinoma treatment
- Tissue Engineering and Regenerative Medicine
- Organ Donation and Transplantation
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Gout, Hyperuricemia, Uric Acid
- Urological Disorders and Treatments
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Renal Diseases and Glomerulopathies
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Retinal Development and Disorders
- Birth, Development, and Health
- Genomics and Chromatin Dynamics
- Lipid metabolism and disorders
- Cellular Mechanics and Interactions
- Developmental Biology and Gene Regulation
- Pediatric Urology and Nephrology Studies
- Liver Disease Diagnosis and Treatment
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Platelet Disorders and Treatments
Kyoto University
2019-2024
RIKEN Center for Biosystems Dynamics Research
2019-2024
Osaka University
2022-2024
Organogenesis (United States)
2022
Murdoch Children's Research Institute
2015-2018
RIKEN Center for Computational Science
2016-2017
Royal Children's Hospital
2015-2016
The University of Queensland
2013-2015
The University of Tokyo
2004-2013
Tokyo University of the Arts
2013
Mutations in SALL4, the human homolog of Drosophila homeotic gene spalt (sal), cause autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation mouse Sall4 leads to lethality during peri-implantation. Growth inner cell mass from knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells proliferated poorly with no aberrant differentiation. Furthermore, demonstrated anorectal heart anomalies syndrome are caused by...
Renal stem or progenitor cells with a multilineage differentiation potential remain to be isolated, and the mechanism of these cell types in kidney development regeneration processes is unknown. In an attempt resolve this issue, we set up vitro culture system using NIH3T3 stably expressing Wnt4 (3T3Wnt4) as feeder layer, which single renal metanephric mesenchyme forms colonies consisting several epithelial that exist glomeruli tubules. We found only strongly Sall1 (Sall1-GFP(high) cells),...
Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population embryonic kidney gives rise all cells within other than collecting duct through mesenchyme-to-epithelial transition, but this is exhausted around time birth. Here, we sought identify conditions under which adult proximal tubule could be directly transcriptionally reprogrammed progenitors. Using combinatorial screen for lineage-instructive...
Abstract Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report development of an exon-skipping therapy using antisense-oligonucleotide (ASO) severe male X-linked syndrome (XLAS). We targeted truncating variants in exon 21 COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, vitro vivo treatment efficacy evaluation. show that skipping enabled trimer formation, leading to...
Abstract In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney tightly regulated by reabsorption and secretion. At least eleven genes have been identified as renal urate transporters. However, it remains unclear whether all tubular cells express same set Here, we show are divided into three distinct cell populations for handling. Analysis healthy kidneys at single-cell resolution revealed that not expressed Only 32% were related to both secretion,...
Currently an in vitro model that fully recapitulates the human embryonic gonad is lacking. Here we describe a defined feeder-free protocol to generate early testis-like cells with ability be cultured as organoid, from induced pluripotent stem cells. This stepwise approach uses small molecules mimic development, upregulation of bipotential markers (LHX9, EMX2, GATA4, and WT1) at day 10 culture, followed by induction testis Sertoli cell (SOX9, WT1, AMH) 15. Aggregation into 3D structures...
Renal transporters play critical roles in predicting potential drug-drug interactions. However, current vitro models often fail to adequately express these transporters, particularly solute carrier proteins, including organic anion (OAT1/3), and cation transporter 2 (OCT2). Here, we developed a hiPSC-derived kidney organoids-based proximal tubule-on-chip (OPTC) model that emulates vivo renal physiology assess function. Compared chips based on immortalized cells, OPTC derived from the two...
Abstract Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining functions tubule epithelial layer—selective filtration and reabsorption. In this report, pseudo cells extracted from human-induced pluripotent stem cell-derived kidney organoids are combined cultured with immortalized cells. It shown that cocultured tissue an impervious epithelium offers improved levels certain transporters, extracellular...
Renal lineages including kidney are derived from intermediate mesoderm, which differentiated a subset of caudal undifferentiated mesoderm. The inductive mechanisms mammalian mesoderm and renal still poorly understood. Mouse embryonic stem cells (mESCs) can be good in vitro model to reconstitute the developmental pathway analyze sequential differentiation. We examined effects Activin A retinoic acid (RA) on induction mESCs under defined, serum-free, adherent, monolayer culture conditions....
An organoid, a self-organizing organ-like tissue developed from stem cells, can exhibit miniaturized three-dimensional (3D) structure and part of the physiological functions original organ. Due to reproducibility complexity ease handling, organoids have replaced real organs animals for variety uses, such as investigations mechanisms organogenesis disease onset, screening drug effects and/or toxicity. The recent advent clearing 3D imaging techniques great potential contributions organoid...
While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen female sex in adulthood, some data showed deterioration kidney function during puberty when production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we that the pubertal hormone surge mice increases susceptibility to ischemia reperfusion injury partly via downregulation insulin-like growth factor 1 receptor (IGF-1R) expression proximal...
Human pluripotent stem cell-derived kidney organoids are expected to be a useful tool for new drug discoveries, however, the immaturation of causes difficulties in recapitulating renal pharmacokinetics using organoids. Here, we performed time-course single-cell RNA sequencing and revealed cell heterogeneity maturation rate proximal tubule. An unbiased analysis identify upstream targets genes that expressed differentially between cells with low high rates higher activation PPARα signaling...