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Download A winding road to pluripotency Shinya Yamanaka CiRA, Kyoto University (Japan)
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A winding road to pluripotency Shinya Yamanaka CiRA, Kyoto University (Japan) Gladstone Institutes (USA) My early days in science Researches led to iPS cells Potential of iPS Cells My early days in science Unexpected results Great mentors PhD Student: Osaka City University Dr. Katsuyuki Miura Dr. Miura’s Hypothesis Platelet activating factor (PAF) Blood pressure Hypothesis Thromboxane A2 inhibitor PAF Time (min) What happened Postdoctoral Fellow: Gladstone Institute Dr. Tom Innerarity Dr. Innerarity’s hypothesis Forced expression of APOBEC1 in liver lowers plasma cholesterol Experiment Liver-specific transgenic mice Liver cancer My early days in science Unexpected results Great mentors Researches that led to iPS cells Liver cancer NAT1 (Novel APOBEC1 Target No1) Identified as a candidate gene responsible for APOBEC1-mediated tumors （Yamanaka et al., 1997) Essential for pluripotency of ES cells （Yamanaka et al., 2000) Embryonic Stem (ES) cells Embryos ES cells Established in mice in 1981 Properties of ES cells Immortality Pluripotency NAT1 PAD Post America Depression Human ES cells hES cell Dr. James Thomson, 1998 Regenerative Medicine & ES Cell Human ES cells Dopaminergic Neuron Parkinson Disease Neural stem cells Spinal cord injury Cardiac cells Cardiac failure Pancreatic cells Diabetics Hepatic cells Hepatic failure Bone cells Osteoporosis Bone marrow cells Leukemia Muscle cells Dystrophy Skin cells Burn Became a principle investigator in Nara (Dec., 1999) Our Research Goal Somatic cells ES-like Stem cells Moral hurdle of human ES cells Sir John Gurdon Somatic cells can be reprogrammed into the embryonic state Dr. Harold Weintraub The transcription factor MyoD turns fibroblasts into muscle Our Research Goal Somatic cells Reprogramming factors ES-like Stem cells Induced Pluripotent Stem (iPS) Cells 4 factors Oct3/4 Sox2 c-Myc Klf4 Skin cells Mouse 2006 ES-like Cells Human 2007 In search of reprogramming factors 1. Collection of 24 candidate factors and others 2. Simple and sensitive assay system 3. Identification of the four factors iPSC Trio Yoshimi Tokuzawa Kazutoshi Takahashi Tomoko Ichisaka Potential of iPS cells Potential of iPS Cells iPS cells Patient Neural cells b-cells Cell Therapy Cardiac cells Hepatocytes Disease Model, Drug Screening Motor Neuron Disease Degenerated Motor Neuron Dead Motor Neuron Atrophying Muscle No effective treatment, because no good disease model Potential of iPS Cells iPS cells Patients Motor neuron Disease models Drug screening Motor Neurons from iPS Cells Control Patient Dr. Haruhisa Inoue, Science Translation al Med 2012 Robotic Drug Screening Potential of iPS Cells iPS cells Patient Neural cells Cell Therapy Cardiac cells Pancreatic cells Hepatocytes Disease Model, Drug Screening Ongoing preclinical studies in Japan iPS cells Dopaminergic neuron Parkinson Retinal cells Macular Degeneration Cardiac cells Cardiac failure Neural Progenitor Spinal cord injury Platelet Platelet deficiency Three scientific streams that led to iPS cells 1962 Cloning in frog Gurdon 1997 Cloning in Sheep Wilmut 2001 ESC fusion Tada 1987 MyoD Weintraub 1981 Mouse ESCs Evans, Martin 2006 iPSCs 1988 LIF Smith 1998 human ESCs Thomson New scientific streams from iPS cells 2006 Mouse iPSCs ? Human iPSC therapy ? 2007 Mouse iPSC therapy Jaenisch 2009 Patient iPSCs Daley Eggan 2008 In vivo direct reprogramming Melton ? Drug discovery w/ iPSCs ? 2012 Mouse therapy by Direct reprogramming Srivastava Center for iPS Cell Research And Application （CiRA), Kyoto Gladstone Institutes, San Francisco 38 Tusen Tack!
