title: Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo.
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.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan matsuoka@endmet.med.osaka-u.ac.jp.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawashima
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.|Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyatsuka
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimo
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Kawamori
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Takebe
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Faculty of Medicine, Geneva, Switzerland.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Herrera
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN.
authors.forename: Roland
authors.initials: R
authors.lastname: Stein
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics*; D054338:Cell Transdifferentiation / Q000235:genetics*; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005934:Glucagon; D018398:Homeodomain Proteins; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C485160:Mafa protein, mouse; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein