Reprogramming with Small Molecules instead of Exogenous Transcription Factors

Table 3

Small molecules (VC6TFZ and 2i) that are used in mouse CiPSC.

Target or signaling pathway	Name and concentration	TF to be replaced	Efficiency	Reference
TGF beta pathway; ALK5 inhibitor	Repsox (616452); 5–10 uM	Sox2, Myc	Essential	Hou et al. (2013) [27]; Ichida et al. (2009) [63]
PKA agonist	Forskolin; 20–50 uM	Oct4 expression (with SKM); Klf2, klf4 expression	Essential	Hou et al. (2013) [27]
WNT pathway regulator, GSK3 beta inhibitor	Chir99021; 10 uM	Sox2, Myc	Essential	Hou et al. (2013) [27]
Histone methylation modulator, lysine methyltransferase EZH2 inhibitor	DENep; 50–100 nM	Increase reprogramming	Essential	Hou et al. (2013) [27]
Not specific	TTNPB; 5 uM	Nuclease receptor signaling modulator	More efficient	Hou et al. (2013) [27]
Not specific	VPA; 0.5 mM	Histone deacetylase inhibitor	More efficient	Hou et al. (2013) [27]
PD0325901: selective MEK/ERK inhibitor; Chir99021: WNT pathway regulator, GSK3 beta inhibitor	2i: PD0325901; 1 uM; Chir99021; 10 uM	Increase Oct4, Nanog, Sox2 expression	More mature	Hou et al. (2013) [27]

Small molecules can substitute for all TFs through epigenetic modifications and signaling pathway regulations. Hou et al. [27] reported that CiPSC generation from mEF was carried out in 3 steps of 16–20 days in VC6TF treatment and then 12–20 days in VC6TFZ and followed by 2i compounds regulations for 1 week. The abbreviations of the small molecules are shown in Tables 1 and 2.