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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399608/
https://www.ncbi.nlm.nih.gov/pubmed/28223284
http://dx.doi.org/10.2337/db16-0887
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author 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
author_facet 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
author_sort Matsuoka, Taka-aki
collection PubMed
description 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.
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spelling pubmed-53996082018-05-01 Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo 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 Diabetes Islet Studies 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. American Diabetes Association 2017-05 2017-02-21 /pmc/articles/PMC5399608/ /pubmed/28223284 http://dx.doi.org/10.2337/db16-0887 Text en © 2017 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Islet Studies
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
Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
title Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
title_full Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
title_fullStr Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
title_full_unstemmed Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
title_short Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
title_sort mafa enables pdx1 to effectively convert pancreatic islet progenitors and committed islet α-cells into β-cells in vivo
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399608/
https://www.ncbi.nlm.nih.gov/pubmed/28223284
http://dx.doi.org/10.2337/db16-0887
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