- Matsuoka TA, Kawashima S, Miyatsuka T, Sasaki S, Shimo N, Katakami N, Kawamori D, Takebe S, Herrera PL, Kaneto H, Stein R, Shimomura I. Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells into β-Cells in Vivo. Diabetes. 2017 Feb 21. PMID: 28223284 [PubMed].
Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in Type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells under conditions of near β-cell loss, a condition similar to T1D. Moreover, human islet α-cells also appear to poised for reprogramming into insulin(+) cells. Here we have generated transgenic mice conditionally expressing the islet β-cell-enriched Mafa and/or Pdx1 transcription factors to examine their potential to transdifferentiate embryonic pan-islet cell Ngn3(+) progenitors and the later glucagon(+) α-cell population into β-cells. Mafa was found to both potentiate the ability of Pdx1 to induce β-cell formation from Ngn3(+) endocrine precursors, and enable Pdx1 to produce β-cells from α-cells. These results provide valuable insight into the fundamental mechanisms influencing islet cell plasticity in vivo.