First Author | Fujita J | Year | 2008 |
Journal | Cell Stem Cell | Volume | 2 |
Issue | 6 | Pages | 595-601 |
PubMed ID | 18522852 | Mgi Jnum | J:149796 |
Mgi Id | MGI:3849144 | Doi | 10.1016/j.stem.2008.04.001 |
Citation | Fujita J, et al. (2008) Caspase activity mediates the differentiation of embryonic stem cells. Cell Stem Cell 2(6):595-601 |
abstractText | Embryonic stem cells (ESCs) are capable of indefinite self-renewal while retaining the ability to differentiate to any of the three germ layers that give rise to all somatic cell types. An emerging view is that a core set of transcription factors, including Oct4, Sox2, and Nanog, form a robust autoregulatory circuit that maintains ESCs in a self-renewing state. To accommodate the capacity of such cells to undergo germ layer-specific differentiation, we predicted a posttranslational mechanism that could negatively regulate these core self-renewal factors. Here we report caspase-induced cleavage of Nanog in differentiating ESCs. Stem cells lacking the Casp3 gene showed marked defects in differentiation, while forced expression of a caspase cleavage-resistant Nanog mutant in ESCs strongly promoted self-renewal. These results link a major component of the programmed cell-death pathway to the regulation of ESC development. |