Divergent co-option of Bcl11 paralogs controls progression through cell fate conversions [scRNA-seq]

Here, we identify the paralogous TFs Bcl11a and Bcl11b as antagonistic regulators of pluripotent reprogramming, neuronal transdifferentiation and oncogenic transformation in vitro. Bcl11a and Bcl11b segregate into cellular intermediates that are respectively permissive or refractory to cell fate conversion (CFC).

Functional perturbation demonstrates that Bcl11a promotes, whereas Bcl11b restricts, progression through cell fate transitions. Bcl11a facilitates efficient exit from intermediate states by promoting loss of fibroblast identity, limiting senescence, supporting epithelial transition during reprogramming and enabling late neuronal program activation during transdifferentiation. Mechanistically, we show that, unlike Bcl11b, Bcl11a is extensively repurposed by Oct4 during reprogramming.