News from CRG
All it takes is one molecule to reprogram an antibody-producing B cell into a scavenging macrophage. This transformation is possible, new evidence shows, because the molecule (C/EBPa, a transcription factor) “short-circuits” the cells so that they re-express genes reserved for embryonic development. The findings appear July 30 in Stem Cell Reports, the journal of the International Society for Stem Cell Research.
“For a long time it was unclear whether forcing cell fate decisions by expressing transcription factors in the wrong cell type could teach us something about what happens normally during physiological differentiation,” says senior study author Thomas Graf, group leader at the Centre for Genomic Regulation in Spain. “What we have now found is that the two processes are actually surprisingly similar.”
Based on experiments led by the first author of the study, Chris van Oevelen, B cell transdifferentiation takes place when C/EBPa binds to two regions of DNA that act as gene expression enhancers. Whereas one of these regions is normally active in immune cells, the other is only turned on when macrophage precursors are ready to differentiate. This indicates that the convergence of these two enhancer pathways can cause the B cell to act like a macrophage precursor, thus triggering the unnatural transdifferentiation.
Stem Cell Reports, van Oevelen et al.: “C/EBPα activates pre-existing and de novo macrophage enhancers during induced pre-B cell transdifferentiation and myeloid lineage specification” http://dx.doi.org/10.1016/j.stemcr.2015.06.007