| First Author | Di Stefano B | Year | 2016 |
| Journal | Nat Cell Biol | Volume | 18 |
| Issue | 4 | Pages | 371-81 |
| PubMed ID | 26974661 | Mgi Jnum | J:236647 |
| Mgi Id | MGI:5806713 | Doi | 10.1038/ncb3326 |
| Citation | Di Stefano B, et al. (2016) C/EBPalpha creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4. Nat Cell Biol 18(4):371-81 |
| abstractText | Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) is typically inefficient and has been explained by elite-cell and stochastic models. We recently reported that B cells exposed to a pulse of C/EBPalpha (Balpha' cells) behave as elite cells, in that they can be rapidly and efficiently reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBPalpha post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell gene silencing and Brd4 for the activation of the pluripotency program. C/EBPalpha also promotes chromatin accessibility in pluripotent cells and upregulates Klf4 by binding to two haematopoietic enhancers. Balpha' cells share many properties with granulocyte/macrophage progenitors, naturally occurring elite cells that are obligate targets for leukaemic transformation, whose formation strictly requires C/EBPalpha. |
