JAK2/STAT3 Directs Cardiomyogenesis Within Murine Embryonic Stem Cells In Vitro

The heart is the first organ to form during development; however, little is known about the mechanisms that control the initial stages of cardiac differentiation. To investigate this process, we used a protein kinase expression screen, in which nonbeating embryonic stem (ES) cells were compared with beating ES cell–derived cardiomyocytes. We found that JAK2 experienced a 70% increase in protein levels within beating areas. Inhibition of JAK2 pharmacologically or by using dominant/negative JAK2 both resulted in diminished beating within embryoid bodies (EBs), whereas gain of function analysis using dominant/positive JAK2 resulted in a significant induction of beating. More important, inhibition of STAT3, a specific target of JAK2, by dominant/negative STAT3 resulted in the virtual complete loss of beating areas. Reverse transcription–polymerase chain reaction and Western analysis of STAT3‐inhibited EBs resulted in lack of expression of several cardiac‐specific genes, many of which contain within their promoter STAT3 DNA‐binding regions. Taken together, the data reveal that the JAK2/STAT3 pathway is essential for initial stages of cardiomyogenesis.