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


ABSTRACT: 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.

SUBMITTER: Matsuoka TA 

PROVIDER: S-EPMC5399608 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Matsuoka Taka-Aki TA   Kawashima Satoshi S   Miyatsuka Takeshi T   Sasaki Shugo S   Shimo Naoki N   Katakami Naoto N   Kawamori Dan D   Takebe Satomi S   Herrera Pedro L PL   Kaneto Hideaki H   Stein Roland R   Shimomura Iichiro I  

Diabetes 20170221 5


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  ...[more]

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