【Date】 Mar. 23 (Fri), 2017 12:00～13:00
【Venue】Conference room, 1st floor,
Institute of Molecular Embryology and Genetics (IMEG)
【Title】“Mechanisms of iPS cell generation and beyond”
【Speaker】Keisuke Kaji
Group Leader,
Professor of Biology of Reprogramming and MRC Senior Non-Clinical Fellow
MRC Centre for Regenerative Medicine, University of Edinburgh
【Abstract】
The generation of induced pluripotent stem cells (iPSCs) achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc, transformed our classical views of the cellular epigenetic landscape and delivered a new concept for cell and tissue engineering. In addition to iPSCs, several other cell types have also been generated by master transcription factor (TF)-mediated transdifferentiation. However, the critical molecular mechanisms amongst diverse cellular identity changes are not well understood. Through the investigation of reprogramming mechanisms, we recently revealed that over-expression of constitutive active Smad3 boosted not only iPSC generation, but also 3 other master TF-mediated conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons. This demonstrated that there were common mechanisms underlying different master TF-mediated cell conversions. To illuminate such mechanisms further, we have recently performed CRISPR/Cas9-mediated genome-wide knockout screening during reprogramming with a lentiviral gRNA library containing 90,000 gRNAs. This screening provided us with ~10 novel reprogramming roadblock genes as well as ~10 novel genes essential for the reprogramming process but not for ES cell self-renewal or fibroblast proliferation. This data set will be a valuable resource to further understand how overexpression of master TFs alters cellular identity, and to achieve more faithful, efficient cell conversions for regenerative medicine.
【Contact】Hitoshi Niwa, Dept of Pluripotent Stem Cell Biology (Ext. 6620)
共催；熊本大学国際先端研究拠点、トランスオミクス医学研究拠点ネットワーク形成事業
