Unveiling a Novel Role for p19Arf in mESC Differentiation Toward the Pancreatic Lineage

However, its involvement in an expanding range of cellular processes reveals that its functions are broader and more complex than initially appreciated. Here, we uncover a previously unrecognized role of p19ARF in endodermal differentiation, specifically in pancreatic lineage specification, using an in vitro differentiation model of mouse embryonic stem cells (mESCs).

Using CRISPR/Cas9-mediated mutagenesis, we show that mESCs with mutations in p19Arf are unable to efficiently differentiate towards pancreatic progenitors. Transcriptomic profiling reveals substantial alterations in gene networks associated not only with lineage commitment but also with cytoskeletal organization and cell morphology. These changes correlate with a disruption in stem cell architecture and suggest the persistence of pluripotency feature in the absence of functional p19Arf.