| First Author | Papadimou E | Year | 2005 |
| Journal | EMBO J | Volume | 24 |
| Issue | 9 | Pages | 1750-61 |
| PubMed ID | 15861132 | Mgi Jnum | J:148069 |
| Mgi Id | MGI:3843435 | Doi | 10.1038/sj.emboj.7600652 |
| Citation | Papadimou E, et al. (2005) Interplay between the retinoblastoma protein and LEK1 specifies stem cells toward the cardiac lineage. EMBO J 24(9):1750-61 |
| abstractText | The molecular mechanisms governing early cardiogenesis are still largely unknown. Interestingly, the retinoblastoma protein (Rb), a regulator of cell cycle, has recently emerged as a new candidate regulating cell differentiation. Rb-/- mice die at midgestation and mice lacking E2f1/E2f3, downstream components of the Rb-dependent transcriptional pathway, die of heart failure. To gain insight into the function of Rb pathway in early cardiogenesis, we used Rb-/- embryonic stem (ES) cells differentiating into cardiomyocytes. Rb-/- cells displayed a dramatic delay in expression of cardiac-specific transcription factors and in turn in the whole process of cardiac differentiation. The phenotype of Rb-/- ES cell-derived cardiomyocytes was rescued by reintroducing Rb in cardiac progenitors, by stimulating the BMP-dependent cardiogenic pathway or by overexpression of Nkx2.5. ES cells deficient in the recently identified factor LEK1, a murine homolog of the cardiomyogenic factor 1, or specific disruption of Rb-LEK1 interaction into the nucleus of differentiating ES cells recapitulated the delay in cardiac differentiation of Rb-/- ES cells. Thus, we provide evidence for a novel Rb/LEK1-dependent and BMP-independent transcriptional program, which plays a pivotal role in priming ES cells toward a cardiac fate. |
