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

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-c...

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Veröffentlicht in:Diabetes (New York, N.Y.) N.Y.), 2017-05, Vol.66 (5), p.1293-1300
Hauptverfasser: Matsuoka, Taka-Aki, Kawashima, Satoshi, Miyatsuka, Takeshi, Sasaki, Shugo, Shimo, Naoki, Katakami, Naoto, Kawamori, Dan, Takebe, Satomi, Herrera, Pedro L, Kaneto, Hideaki, Stein, Roland, Shimomura, Iichiro
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Sprache:eng
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Zusammenfassung: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-positive 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-positive progenitors and the later glucagon-positive α-cell population into β-cells. Mafa was found to both potentiate the ability of Pdx1 to induce β-cell formation from Ngn3-positive 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.
ISSN:0012-1797
1939-327X
DOI:10.2337/db16-0887