| First Author | Sunadome K | Year | 2014 |
| Journal | Mol Cell | Volume | 54 |
| Issue | 3 | Pages | 526-35 |
| PubMed ID | 24703953 | Mgi Jnum | J:213621 |
| Mgi Id | MGI:5585392 | Doi | 10.1016/j.molcel.2014.03.005 |
| Citation | Sunadome K, et al. (2014) Antagonism between the master regulators of differentiation ensures the discreteness and robustness of cell fates. Mol Cell 54(3):526-35 |
| abstractText | The discreteness of cell fates is an inherent and fundamental feature of multicellular organisms. Here we show that cross-antagonistic mechanisms of actions of MyoD and PPARgamma, which are the master regulators of muscle and adipose differentiation, respectively, confer robustness to the integrity of cell differentiation. Simultaneous expression of MyoD and PPARgamma in mesenchymal stem/stromal cells led to the generation of a mixture of multinucleated myotubes and lipid-filled adipocytes. Interestingly, hybrid cells (i.e., lipid-filled myotubes) were not generated, suggesting that these differentiation programs are mutually exclusive. Mechanistically, although exogenously expressed MyoD was rapidly degraded in adipocytes through ubiquitin-proteasome pathways, exogenously expressed PPARgamma was not downregulated in myotubes. In PPARgamma-expressing myotubes, PPARgamma-dependent histone hyperacetylation was inhibited in a subset of adipogenic gene loci, including that of C/EBPalpha, an essential effector of PPARgamma. Thus, the cross-repressive interactions between MyoD- and PPARgamma-induced differentiation programs ensure discrete cell-fate decisions. |
