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- Title
Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo.
- Authors
Taka-aki Matsuoka; Satoshi Kawashima; Takeshi Miyatsuka; Shugo Sasaki; Naoki Shimo; Naoto Katakami; Dan Kawamori; Satomi Takebe; Herrera, Pedro L.; Hideaki Kaneto; Stein, Roland; Iichiro Shimomura; Matsuoka, Taka-Aki; Kawashima, Satoshi; Miyatsuka, Takeshi; Sasaki, Shugo; Shimo, Naoki; Katakami, Naoto; Kawamori, Dan; Takebe, Satomi
- Abstract
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.
- Subjects
TYPE 1 diabetes; PROGENITOR cells; GLUCAGON; CELL populations; ISLANDS of Langerhans; PROTEIN metabolism; ANIMAL experimentation; CELL differentiation; CELL physiology; IMMUNOHISTOCHEMISTRY; MICE; NERVE tissue proteins; PROTEINS; RESEARCH funding; STEM cells; CYTOMETRY
- Publication
Diabetes, 2017, Vol 66, Issue 5, p1293
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0887