Send to

Choose Destination
Cell Cycle. 2012 Jul 15;11(14):2739-46. doi: 10.4161/cc.21119. Epub 2012 Jul 15.

C/EBPα bypasses cell cycle-dependency during immune cell transdifferentiation.

Author information

Gene Regulation, Stem Cells and Cancer Program, Center for Genomic Regulation and Pompeu Fabra University, Barcelona, Spain.


Our earlier work has shown that pre-B cells can be converted into macrophage-like cells by overexpression of the transcription factor C/EBPα or C/EBPβ with high efficiency. Using inducible pre-B cell lines, we have now investigated the role of cell division during C/EBP-induced reprogramming. The majority of cells reprogrammed by C/EBPα incorporated BrdU before arresting at G(0), and all C/EBPβ-induced cells incorporated the compound. This contrasts with reports from other systems where transdifferentiating cells essentially do not divide. Although inhibition of DNA synthesis led to an impairment of C/EBPα-induced transdifferentiation, sorted G(0)/G(1) and G(2)/M fractions showed no significant differences in their reprogramming kinetics. In addition, knocking-down p53 did not accelerate the transdifferentiation frequency, as it has been described for reprogramming of induced pluripotent (iPS) cells. Time-lapse experiments showed that, after C/EBPα induction, approximately 90% of cells divide once or twice, while 8% do not divide at all before acquiring a macrophage phenotype, supporting our BrdU incorporation results. Importantly, the non-dividing cell subset expressed the highest levels of C/EBPα and was the fastest in differentiating, suggesting that high levels of C/EBPα accelerate both the switching process and the cells' growth arrest. Our data show that traversing the cell cycle is not strictly required for pre-B cell to macrophage conversion and provides new evidence for the notion that the mechanisms of transcription factor induced transdifferentiation and iPS cell reprogramming differ.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center