Our iPSC Differentiation Technology

Fast and easy iPSC differentiation enables more effective ways to model human biology and disease, opening the door to a wealth of applications.

The Promise of iPSCs

Human induced pluripotent stem cells (iPSCs) have been expected to drive the stem cell revolution by giving researchers an almost alchemical ability to transform one type of cell into virtually any other type of cell. Instead of hunting for rare stem cells, researchers could create iPSCs and then differentiate the iPSCs into neurons, skeletal muscle cells, hepatocytes, and so on, enabling studies on impossible-to-obtain human cells, creating an unlimited supply of genetically-identical human cells for tightly-controlled bioproduction and high-throughput screening, and developing novel cell-based therapeutics.

In addition, by providing a better model for human biology and disease than primary cells derived from animal models, human iPSCs can reduce our dependence on the use of animals for research.

Bar graph depicting variations in published differentiation time scales for iPSC differentiation

The Challenge of iPSCs

However, iPSCs have not had as significant an impact on our understanding of human biology or the advancement of human health as many scientists might have hoped for, as the iPSC differentiation process has proven to be technically challenging, labor-intensive, and time-consuming. Few labs can consistently differentiate a variety of iPSC lines into healthy, functional, and pure populations of target cells.

The Technology that Brings the Full Promise of iPSCs to Every Lab

Elixirgen Scientific has developed an iPSC differentiation technology that makes it possible for any lab to quickly and easily generate iPSC-derived cells in as little as 1-2 weeks. Our transcription factor-based approach leaves the genome untouched, maintaining the physiological relevance of the cells, and is consistently successful for the reliable generation of target tissue. Available as differentiation kits that deliver the transcription factors through equally efficient mRNA or non-integrating Sendai virus formats, Elixirgen Scientific’s iPSC differentiation technology puts all the advantages of iPSC-derived cells into the hands of every lab.

Transcription-factor Based iPSC Differentiation

Our technology is based on over 20 years of research conducted in the laboratory of Elixirgen Scientific’s founder and Chief Scientific Officer, Minoru Ko, M.D., Ph.D., at the National Institute of Aging (1998-2011) and Keio University School of Medicine (2012-present).

The approach is conceptually very simple—introduce a specific set of transcription factors to iPSCs/ESCs at the appropriate times and in the appropriate media to promote differentiation into the desired cell type. The power behind Elixirgen Scientific’s approach is the hard work spent identifying the right transcription factors, the right time, and the right media.

The Scientific History of Our iPSC Differentiation Technology

While at the National Institute of Aging, Dr. Ko used mouse ES cells to establish and demonstrate the principles of the transcription factor-based iPSC differentiation approach that Elixirgen Scientific’s scientists use today. His lab also generated a large number of mouse ES cell clones and gene expression profiles that are still in use today and available to the research community through the Coriell Cell Repository.

The research at Keio University extended this work further into the more biologically relevant human ES and iPS cells. These technologies have been exclusively licensed from Keio University to Elixirgen Scientific.

Publications

Nakatake Y, Ko SBH, Sharov AA, Wakabayashi S, Murakami M, Sakota M, Chikazawa N, Ookura C, Sato S, Ito N, Ishikawa-Hirayama M, Mak SS, Jakt LM, Ueno T, Hiratsuka K, Matsushita M, Goparaju SK, Akiyama T, Ishiguro KI, Oda M, Gouda N, Umezawa A, Akutsu H, Nishimura K, Matoba R, Ohara O, Ko MSH.

Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors. Cell Rep. 2020 May 19;31(7). PubMed

Akiyama T, Sato S, Chikazawa-Nohtomi N, Soma A, Kimura H, Wakabayashi S, Ko SBH, Ko MSH.

Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing. Sci Rep. 2018 Jan 19;8(1):1189. PubMed

Matsushita M, Nakatake Y, Arai I, Ibata K, Kohda K, Goparaju SK, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Kanai T, Yuzaki M, Ko MSH.

Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors. Biochem Biophys Res Commun. 2017 Aug 19;490(2):296-301. PubMed

Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Ko MSH.

Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells. Stem Cells Int. 2017;2017:7215010. PubMed

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

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. 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

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

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

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

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

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

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