The Science Behind Our Technology
Our technology platform relies on key transcription factor (TF) genes, a combination of which determines the identity of cells. These TFs are so powerful that they can rapidly and efficiently differentiate human pluripotent stem cells, such as ES cells and iPS cells, into specific cell types, such as neurons and muscles. These TFs are introduced into cells in the form of RNAs – either Synthetic mRNAs or Sendai virus RNA vectors, and thus, they do not leave any footprint on the genome.
Our platform is based on the technologies that have been developed in the laboratory of Minoru S.H. Ko, M.D., Ph.D. at the National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, Maryland (1998-2011) and Keio University School of Medicine, Shinjuku, Tokyo (2012-present). The project at NIH established and demonstrated the principles using mouse ES cells (References 1-6). The project has also generated a large number of mouse ES cell clones and gene expression profiles (Link): these mouse ES cell clones have been made available to the research community thorough the Coriell Cell Repository (Link). The project at Keio extended the work to human ES and iPS cells (References 7-9). These technologies have been exclusively licensed from Keio University (see the News section).
- Nishiyama A, Xin L, Sharov AA, Thomas M, Mowrer G, Meyers E, Piao Y, Mehta S, Yee S, Nakatake Y, Stagg C, Sharova L, Correa-Cerro LS, Bassey U, Hoang H, Kim E, Tapnio R, Qian Y, Dudekula D, Zalzman M, Li M, Falco G, Yang HT, Lee SL, Monti M, Stanghellini I, Islam MN, Nagaraja R, Goldberg I, Wang W, Longo DL, Schlessinger D, Ko MS. (2009). Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009 Oct 2;5(4):420-33. [PubMed] [Cell Stem Cell]
- Correa-Cerro LS, Piao Y, Sharov AA, Nishiyama A, Cadet JS, Yu H, Sharova LV, Xin L, Hoang HG, Thomas M, Qian Y, Dudekula DB, Meyers E, Binder BY, Mowrer G, Bassey U, Longo DL, Schlessinger D, Ko MS. (2011). Generation of mouse ES cell lines engineered for the forced induction of transcription factors. Sci Rep 2011; 1: 167. [PubMed] [Scientific Reports].
- Nishiyama A, Sharov AA, Piao Y, Amano M, Amano T, Hoang HG, Binder BY, Tapnio R, Bassey U, Malinou JN, Correa-Cerro LS, Yu H, Xin L, Meyers E, Zalzman M, Nakatake Y, Stagg C, Sharova L, Qian Y, Dudekula D, Sheer S, Cadet JS, Hirata T, Yang HT, Goldberg I, Evans MK, Longo DL, Schlessinger D, Ko MS. (2013). Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci Rep. 2013;3:1390. [PubMed] [Scientific Reports]
- Yamamizu K, Piao Y, Sharov AA, Zsiros V, Yu H, Nakazawa K, Schlessinger D, Ko MS. Identification of transcription factors for lineage-specific ESC differentiation. Stem Cell Reports. 2013 Nov 27;1(6):545-59.[PubMed] [Stem Cell Reports]
- Yamamizu K, Sharov AA, Piao Y, Amano M, Yu H, Nishiyama A, Dudekula DB, Schlessinger D, Ko MS. (2016). Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines. Sci Rep. 2016 May 6;6:25667.[PubMed] [Scientific Reports]
- Teratani-Ota Y, Yamamizu K, Piao Y, Sharova L, Amano M, Yu H, Schlessinger D, Ko MS, Sharov AA. Induction of specific neuron types by overexpression of single transcription factors. In Vitro Cell Dev Biol Anim. 2016 Oct;52(9):961-973. [PubMed]
- Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SB, Ko MS. Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells. Development. 2016 Oct 15;143(20):3674-3685. [PubMed] [Development]
- Hirayama M, Ko SB, Kawakita T, Akiyama T, Goparaju SK, Soma A, Nakatake Y, Sakota M, Chikazawa-Nohtomi N, Shimmura S, Tsubota K, Ko MS. Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells. npj Aging and Mechanisms of Disease 2017; 3: 1. [Link]
- Goparaju SK, Kohda K, Ibata K, Soma A, Nakatake Y, Akiyama T, Wakabayashi S, Matsushita M, Sakota M, Kimura H, Yuzaki M, Ko SB, Ko MS. Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. Sci Rep. 2017 Feb 13;7:42367.[PubMed] [Scientific Reports]