News from CRG
A team led by Thomas Graf from the CRG has identified the protein C/EBPa as a surprising connection between cell reprogramming, blood cell formation and blood cancer. In previous work, the Graf laboratory found that introduction of C/EBPa into mouse lymphocytes, which are immune cells, almost magically turns them into elite cells for reprogramming by the Yamanaka cocktail. Both C/EBPa and the four Yamanaka factors are so called transcription factors: proteins that bind to specific sequences in the DNA, thereby turning the activity of genes embedded in chromatin on or off. Changes in gene expression are essential for cell reprogramming, since genes important for stem cell functions must be turned on, while genes important for the starting cells or its specialization must be turned off.
In this work published in Nature Cell Biology, Bruno Di Stefano in Graf’s group, in collaboration with Janus Jakobsen and Bo Porse from the Biotech Research and Innovation Centre at the University of Copenhagen, Samuel Collombet and Denis Thieffry from the Ecole Normal Superieure in Paris, and Michael Wierer and Matthias Mann from the Max Planck Institute in Martinsried, found that C/EBPa changes the chromatin and the proteome of B-lymphocytes to make it receptive to the action of the Yamanaka factors. “We have made major advances to understand how C/EBPa contributes to cell reprogramming, allowing us to obtain elite cells in a highly effective manner. We also found that such artificially created elite cells are very similar to white blood cell progenitors in the bone marrow called ‘GMPs’ or myeloblasts, which themselves require C/EBPa for their formation,” explains principal investigator Thomas Graf.
Di Stefano et al. “C/EBPα creates elite cells for iPS cell reprogramming by upregulating Klf4 and post-transcriptionally increasing Lsd1 and Brd4 levels” Nature Cell Biology. 2016. http://dx.doi.org/10.1038/ncb3326