Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds

By Danwei Huangfu, René Maehr, Wenjun Guo, A. Eijkelenboom, Melinda E. Snitow, Alice E. Chen, D. Melton. 2008

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In Molecular Biology

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Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon (2009, positive): “We transfected 10 6 MEFs with a transfection efficiency of approximately 10 % and obtained approximately 1,000 colonies, therefore, the overall reprogramming efficiency is approximately 1%, virtually equivalent to the retroviral method.”
Pluripotency: Toward a gold standard for human ES and iPS cells (2009, background): “…to produce iPS cells suggest that the challenge of genomic integration can be overcome (Table 4) (Okita et al., 2007; JOURNAL OF CELLULAR PHYSIOLOGY Huangfu et al., 2008; Lowry and Plath, 2008; Stadtfeld et al., 2008). iPS technology has opened the door to a future of directed differentiation…”
A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. (2010, background): “Remarkably, a series of compounds including TGF-b (transforming growth factor b) inhibitors have been identified that accelerate or improve the reprogramming (Esteban et al., 2010; Huangfu et al., 2008; Ichida et al., 2009; Maherali and Hochedlinger, 2009; Mikkelsen et al., 2008), and this may shed ”
Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. (2010, methodology): “Notably, Vc had a more potent effect in increasing GFP cells in SKO-infected MEFs than the widely used histone deacetylase inhibitor valproic acid (VPA) (Huangfu et al., 2008), and the combination of both was additive (Figure 1E, middle), suggesting that they act through different mechanisms.”
Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 (2008, background): “Another approach that we and others have explored is the use of small-molecule chemicals or growth factors in combination with the genetic factors to reprogram mouse somatic cell”
Direct cell reprogramming is a stochastic process amenable to acceleration (2009, background): “17 Huangfu, D. et al., Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26 (7), 795-797 (2008).”
Hypoxia enhances the generation of induced pluripotent stem cells. (2009, background): “Many efforts have been made to find other factors or small molecules that facilitate the reprogramming process (Huangfu et al., 2008; Shi et al., 2008b).”
Senescence impairs successful reprogramming to pluripotent stem cells. (2009, background): “…alterations have been identified such as histone deacetylase (HDAC) inhibitors, especially valproic acid (VPA), which have been shown to noticeably increase reprogramming efficiency in MEFs (100-fold for OSK and 50-fold for OSKM) and in human fibroblasts (20-fold) (Huangfu et al., 2008).”
Highly efficient reprogramming to pluripotency and directed differentiation of human cells using synthetic modified mRNA (2010, methodology): “, 2009), and we supplemented the media with valproic acid (VPA), a histone deacetylase inhibitor that has been reported to increase reprogramming efficiency (Huangfu et al., 2008).”