Most reports have used fibroblasts as donor cells for reprogramming experiments. Fibroblasts, however, are ill-defined and heterogeneous cell preparations. Thus, in those experiments, the exact cells undergoing fate conversion remained unclear. In a quest to better define the cell of origin for iN cell reprogramming, we explored better defined and genetically tractable cell types. At the same time, we were curious whether a cell lineage derived from the endodermal germ layer could be converted into neurons. Using a defined genetic labeling and cell lineage tracing system, we unequivocally demonstrated that endodermal cells can be converted directly into iN cells (representing ectoderm) using the same BAM pool of transcription factors [40]. This suggested that – unlike predominantly assumed in the field – the degree of developmental relationship might not be the most important parameter whether cell fate conversions are feasible. The defined cell of origin also allowed us to address the question of the degree of reprogramming achievable in iN cells. We particularly focused on how well the donor cell transcriptional program is silenced in resulting iN cells. Using both bulk
