Promyelocytic Leukemia (PML) protein is an essential regulator of stem cell pluripotency and somatic cell reprogramming

Promyelocytic Leukemia Protein (PML) was first identified as a fusion product with the retinoic acid receptor alpha in Acute Promyelocytic Leukemia (APL). Although PML has previously been studied in cancer progression and various physiological processes, little is known about its functions in Embryonic Stem Cells (ESC). Here, we report that PML contributes to the maintenance of the ESC self-renewal by controlling the cell-cycle and sustaining the expression levels of crucial pluripotency factors. Transcriptomic analysis showed that the ablation of PML renders ESC prone to exit from the naïve and acquire a primed-like pluripotent cell state. During differentiation PML influences cell fate decision by regulation of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced Pluripotent Stem Cells (iPSC) by inhibiting the TGFβ pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC pluripotency and somatic cell reprogramming. gene expession profile of ESCs and differentiated EBs D4 in the presence or deletion of PML. Samples were selected for RNA extraction and hybridization on Affymetrix microarrays.