Abstract: Recent breakthroughs in generating induced pluripotent stem cells (iPSCs) using four defined
factors have revealed the potential utility of stem cells in biological research and clinical applications.
However, the low efficiency and slow kinetics of reprogramming related to producing these cells and
underlying safety issues, such as viral integration and genetic and epigenetic abnormalities of iPSCs,
hamper the further application of iPSCs in laboratory and clinical settings. Previous studies have suggested
that reprogramming efficiency can be enhanced and that reprogramming kinetics can be accelerated
by manipulating epigenetic status. Herein, we review recent studies on the application of epigenomemodifying
small molecules in enhancing reprogramming and functionally replacing some reprogramming
factors.We mainly focus on studies that have used small molecules to interfere with epigenome-modifying
enzymes, such as DNA methyltransferase, histone acetyltransferase, and histone methyltransferase. The
potential use of these small molecules in inducing iPSCs and new ways to identify small molecules of
higher potency and fewer side effects are also discussed