CCAAT/enhancer binding protein-α (C/EBPα) induces transdifferentiation of B 
cells into macrophages at high efficiencies and enhances reprogramming into 
induced pluripotent stem (iPS) cells when co-expressed with the transcription 
factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM). However, how 
C/EBPα accomplishes these effects is unclear. Here we find that in mouse primary 
B cells transient C/EBPα expression followed by OSKM activation induces a 
100-fold increase in iPS cell reprogramming efficiency, involving 95% of the 
population. During this conversion, pluripotency and epithelial-mesenchymal 
transition genes become markedly upregulated, and 60% of the cells express Oct4 
within 2 days. C/EBPα acts as a 'path-breaker' as it transiently makes the 
chromatin of pluripotency genes more accessible to DNase I. C/EBPα also induces 
the expression of the dioxygenase Tet2 and promotes its translocation to the 
nucleus where it binds to regulatory regions of pluripotency genes that become 
demethylated after OSKM induction. In line with these findings, overexpression 
of Tet2 enhances OSKM-induced B-cell reprogramming. Because the enzyme is also 
required for efficient C/EBPα-induced immune cell conversion, our data indicate 
that Tet2 provides a mechanistic link between iPS cell reprogramming and B-cell 
transdifferentiation. The rapid iPS reprogramming approach described here should 
help to fully elucidate the process and has potential clinical applications.