In a study published in the latest issue of Stem Cell Reports José Bragança and his team demonstrated that the transcriptional regulator CITED2 – essential for mammalian heart development – plays an important role in the early steps of cardiac lineage commitment of mouse embryonic stem cells (ESC). Of particular interest, the researchers showed for the first time that Cited2 and Isl1, a key transcription factor in the development of secondary heart field-derived structures and a marker of secondary heart field cardiac progenitors, have a privileged interaction at the genetic and protein levels. Indeed, they showed that Cited2 is directly recruited to the promoter of the Isl1 gene, and promotes Isl1 expression when overexpressed, while Cited2-depletion impairs Isl1 expression. Furthermore, the investigation revealed that Cited2 expression is enriched in cardiac progenitor cells originated from ESC differentiation, or isolated from mouse embryonic hearts. This team also demonstrated that the proteins ISL1 and CITED2 interact physically in vitro and ex vivo. Moreover, they showed that the ISL1-CITED2 interaction is synergistically functional, and promotes cardiomyocyte differentiation from ESC.
To achieve these results, that significantly increase the knowledge about ESC commitment towards cardiac cell lineage and highlights the importance of Cited2 in this process, Bragança and his team used embryonic stem cells to better understand the function of this transcriptional regulator in the cardiogenic processes.
Since there is a great interest in deriving cardiac progenitors and cardiomyocytes from pluripotent stem cells for therapeutic purposes, the results presented in this paper may be instrumental for the development of novel strategies heading in this direction.
Read the paper here.