| Autor: |
Di Stefano, Bruno, Collombet, Samuel, Jakobsen, Janus Schou, Wierer, Michael, Sardina, Jose Luis, Lackner, Andreas, Stadhouders, Ralph, Segura-Morales, Carolina, Francesconi, Mirko, Limone, Francesco, Mann, Matthias, Porse, Bo, Thieffry, Denis, Graf, Thomas |
| Zdroj: |
Nature Cell Biology; April 2016, Vol. 18 Issue: 4 p371-381, 11p |
| Abstrakt: |
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/EBPα (Bα′ 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/EBPα 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/EBPα also promotes chromatin accessibility in pluripotent cells and upregulates Klf4 by binding to two haematopoietic enhancers. Bα′ cells share many properties with granulocyte/macrophage progenitors, naturally occurring elite cells that are obligate targets for leukaemic transformation, whose formation strictly requires C/EBPα. |
| Databáze: |
Supplemental Index |
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