Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet -Cells Into -Cells In Vivo

Among the therapeutic avenues being explored for replacement of the functional islet -cell mass lost in type 1 diabetes (T1D), reprogramming of adult cell types into new -cells has been actively pursued. Notably, mouse islet -cells will transdifferentiate into -cells under conditions of near -cell loss, a condition similar to T1D. Moreover, human islet -cells also appear to poised for reprogramming into insulin-positive cells. Here we have generated transgenic mice conditionally expressing the islet -cell-enriched Mafa and/or Pdx1 transcription factors to examine their potential to transdifferentiate embryonic pan-islet cell Ngn3-positive progenitors and the later glucagon-positive -cell population into -cells. Mafa was found to both potentiate the ability of Pdx1 to induce -cell formation from Ngn3-positive endocrine precursors and enable Pdx1 to produce -cells from -cells. These results provide valuable insight into the fundamental mechanisms influencing islet cell plasticity in vivo.