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.
Huangfu
Danwei
D
Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Maehr
René
R
Guo
Wenjun
W
Eijkelenboom
Astrid
A
Snitow
Melinda
M
Chen
Alice E
AE
Melton
Douglas A
DA
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