Role of C/EBPa in inducing the formation of pluripotent cells
Somatic cell reprogramming into pluripotent stem cells induced by Oct4, Sox2, Klf4 and Myc (OSKM) occurs at low frequencies and with a considerable delay, involving a stochastic phase. Earlier work by the Jaenisch lab showed that co-expression of C/EBPa with OSKM enhances reprogramming (Hanna et al., Cell, 2008).
We now discovered that a pulse of C/EBPa, rather than its continuous expression, induces a very rapid and highly efficient reprogramming to pluripotency, essentially overcoming the stochastic phase. The cells simultaneously activate mesenchymal-epithelial transition and pluripotency genes to high levels within 2 days and are capable of differentiating into all three germ layers in vitro and in vivo.
We are currently investigating the molecular mechanisms of This C/EBPa mediated enhancement of cell reprogramming to pluripotency.