Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds.
Reprogramming of mouse and human somatic cells can be achieved by ectopic expression of transcription factors, but with low efficiencies. We report that DNA methyltransferase and histone deacetylase (HDAC) inhibitors improve reprogramming efficiency. In particular, valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a reporter. VPA also enables efficient induction of pluripotent stem cells without introduction of the oncogene c-Myc.
Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Danwei
D
Huangfu
René
R
Maehr
Wenjun
W
Guo
Astrid
A
Eijkelenboom
Melinda
M
Snitow
Alice E
AE
Chen
Douglas A
DA
Melton
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D056572:Histone Deacetylase Inhibitors; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014635:Valproic Acid / Q000008:administration & dosage*
D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D004248:DNA (Cytosine-5-)-Methyltransferases