JST Basic Research Programs
CREST

Chief Researcher Toshio Suda

Research area "Fundamental technologies for medicine concerning the generation and regulation of induced pluripotent stem (iPS) cells"

As part of a system for encouraging innovation that will lead to societal and economical reforms, "Core Research for Evolutional Science and Technology" (CREST) is designed to promote targeted basic research in strategically prioritized fields, and to create innovative new technologies that will lead to the future growth of science and technologies and the creation of new industries.
In the research area "Fundamental technologies for medicine concerning the generation and regulation of induced pluripotent stem (iPS) cells", a CREST-type research project, emphasis is placed on the creation of the seeds of promising technologies, including the examination of the mechanisms of cell reprogramming, research on new technologies for creating and reprogramming iPS cell, and the development of techniques of differentiation induction into stem or tissue cells.
Following public invitation and selection, a number of research subjects were adopted (ten for the year 2008, seven for the year 2009, six for the year 2010) during the period of three years from the year 2008, and a variety of stem cell studies have been performed by research teams.
Since we have been promoting top-level basic research in the above-mentioned scientific fields, we named them CREST (Core Research for Evolutional Science and Technology), which means "top" or "summit".

Research achievements

Successful repair of genes in iPS cells derived from patients with muscular dystrophy

Picture:Successful repair of genes in iPS cells derived from patients with muscular dystrophy

The research team led by Professor Oshimura, Tottori University, succeeded in completely repairing dystrophin genes without damaging the genome by introducing an artificial chromosome vector carrying the dystrophin gene (a causative gene) into the skin cells of patients with Duchenne muscular dystrophy ? a genetic disease associated with gradual muscular atrophy and muscle weakness. The research team also generated iPS cells from the above-mentioned cells and differentiated them into muscle cells to confirm the function of repaired dystrophin genes. This was the first case that dystrophin genes were repaired in the iPS cells obtained from muscular dystrophy patients, which is expected to lead to new gene therapies.

Creation of lymphocytes from iPS cells effective for immunotherapy
- The world's first research team to create optimum NKT cells with anticancer effects -

Creation of lymphocytes from iPS cells effective for immunotherapy

In an experiment using mice, the research team led by Group Director Koseki, RIKEN, generated iPS cells from natural killer T (NKT) cells, a type of anticancer immunocyte, and also succeeded in producing only NKT cells from these iPS cells. The creation of immunocytes from skin-derived iPS cells has the disadvantage of generating a large amount of other cells than targeted ones, leading to a decrease in the efficiency of iPS cell production. On the other hand, it has been confirmed that NKT cells are produced in a very efficient manner from NKT cell-derived iPS cells. It has long been a challenge to produce a large number of NKT cells. We believe that the new technology, which helps activate NKT cells to attack cancer cells, will provide a significant improvement in anti-cancer treatment.

Research Area advisors

Name Title / Affiliation
Isao Ishida Professor, Faculty of Pharmacy, Teikyo Heisei University
Hiroyuki Sasaki Professor, Medical Institute of Bioregulation, Kyushu University
Mikiko Shiomi Associate Professor, School of Medicine, Keio University
Yoshimi Takai Professor, School of Medicine, Kobe University
Masatoshi Takeichi Director, Center for Developmental Biology, RIKEN
Toru Nakano Professor, Graduate School of Frontier Biosciences/Graduate School of Medicine, Osaka University
Yoshihide Hayashizaki Director, Omics Science Center, RIKEN
Kohei Miyazono Professor, Graduate School of Medicine, The University of Tokyo

Frow of CREST

Chart:Frow of CREST

Research Themes

2008f.y. Principle Investigators

Research Director (affiliation) Research Themes Keywords
Shunsuke Ishi
Chief Scientist, RIKEN
Mechanism of reprogramming by germ cell histones Histone, Fertilized egg, Pluripotency
Atsushi Iwama
Professor, Chiba University
Manipulation of epigenetic status of hematopoietic stem cells for regenerative medicine Hematopoietic stem cell, Epigenetics, Polycomb gene
Akihiko Okuda
Professor, Saitama Medical University
Invention of devices for elevating security level of iPS cells through understanding the molecular mechanisms of iPS cell generation Security, c-Myc, Molecular mechanism, ES cells, Pluripotency
Mitsuo Oshimura
Professor, Tottori University
Creation of iPS cells using human artificial chromosomes and genetic/regenerative medicine Towards ideal iPS cells for gene therapy and regenerative medicine using a human artificial chromosome (HAC)
Haruhiko Koseki
Group Leader, RIKEN
Isolation of molecular markers that represent pluripotency and tumorigenicity of human iPS cells Immunocytes (B cells, NKT cells), Safety evaluation
Hideyuki Saya
Professor, Keio University
Analysis of abnormal regulation of cell differentiation and drug development research by using induced cancer stem cells Cancer stem cells, Induced cancer stem cells (iCSC), Drug discovery research, Niche, Osteosarcoma
Takashi Shinohara
Professor, Kyoto University
Analysis of reprogramming mechanism of Germline stem cells Germ stem cells, Germ cells, Pluripotency, Spermatogenesis, mGS cells
Satoru Senju
Associate Professor, Kumamoto University
Research on iPS Cell-Derived Dendritic Cells and Macrophages Aiming at Clinical Application Dendritic cells, Macrophages, Immunotherapy, Cancer, Alzheimer's disease
Hitoshi Niwa
Project Leader,RIKEN
Analysis of the transcription factor network governing establishment of pluripotency in somatic cells Transcription factors, Network, Pluripotency, Exogenous/endogenous genes
Yoshihiro Yoneda
Professor, Osaka University
A novel and efficient method of cellular reprogramming using human artificial chromosomes (HACs) Artificial chromosomes, Information exchange between nucleus and cytoplasm, Nuclear transport factors

2009f.y. Principle Investigators

Research Director (affiliation) Research Themes Keywords
Haruhisa Inoue
Associate Professor, Kyoto University
Development of personalized preventive medicine toward neurodegenerative diseases based on pathomechanistic insight explored by iPS cell technology Disease-specific iPS cells, Neurodegenerative disorders, Preventive medicine
Takumi Era
Professor, Kumamoto University
Analysis of molecular basis of stem cell generation using guided differentiation of iPS cell into tissue stem cells Mesenchymal stem cells, Hematopoietic stem cells, Renal precursor cells, Molecular mechanism in development/differentiation
Michinori Saitou
Professor, Kyoto University
A comprehensive analysis of the mechanism underlying the genome-wide epigenetic reprogramming in the germ cell lineage and its application Germ line cells, Cell lineage differentiation, Genome reprogramming
Nobuyuki Takakura
Professor, Osaka University
Analysis of molecular mechanisms involved in physiological cell reprogramming Reprogramming in vivo, Hematopoietic stem cells, Tissue regeneration
Yoshiko Takahashi
Professor, Nara Institute of Science and Technology
In vivo directed reprogramming of neural crest cells Reprogramming in vivo, Neural crest cells, Transcriptional factors
Noriyuki Tsumaki
Associate Professor, Osaka University
Directed induction of chondrogenic stem / progenitor cells from dermal fibroblast culture by defined factors Direct reprogramming, Precursor chondrocytes, Treatment for cartilage disorders
Eisuke Nishida
Professor, Kyoto University
Molecular mechanisms of transcriptional regulation in cell reprogramming and differentiation Transcriptional factors, Gene expression patterns, Bioinformatics

2010f.y. Principle Investigators

Research Director (affiliation) Research Themes Keywords
Masaki Ieda
Lecturer, Keio University
Direct reprogramming of fibroblasts into cardiomyocytes by defined factors and its application to potential regenerative therapies Direct reprogramming, Myocardial induction, iCM cells
Mineo Kurokawa
Professor, The University of Tokyo
Search for pathogenesis and novel therapeutics of hematological malignancies based on generation of iPS cells from primary tumor cells Disease-specific iPS cells, Leukemia, Analysis of pathogenic mechanisms
Yutaka Hanazono
Professor, Jichi Medical University
The generation of high-quality human iPS cells and their characterization Ground state, Mouse/human iPS cells, Large animals, Quality improvement
Atsushi Miyajima
Professor, The University of Tokyo
Construction of functional liver tissues using iPS cells Hepatocyte induction, Three-dimensional organization, Creation of hepatic tissue
Ken-ichi Yamamura
Professor, Kumamoto University
Establishment of the mouse model with human liver derived from iPS cells and its use for experimental therapy Hepatocyte induction, Humanized liver mouse, Pathological models
Minoru Yoshida
Group Director, RIKEN
Chemical regulation of nuclear epigenome and mitochondrial genome Exploratory research on compounds, Chemical epigenetics, Mitochondria genome

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