MafA is critical for maintenance of the mature beta cell phenotype in mice

Diabetologia. 2015 Mar;58(3):566-74. doi: 10.1007/s00125-014-3464-9. Epub 2014 Dec 13.


Aims/hypothesis: The plasticity of adult somatic cells allows for their dedifferentiation or conversion to different cell types, although the relevance of this to disease remains elusive. Perturbation of beta cell identity leading to dedifferentiation may be implicated in the compromised functions of beta cells in diabetes, which is a current topic of islet research. This study aims to investigate whether or not v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), a mature beta cell marker, is involved in maintaining mature beta cell phenotypes.

Methods: The fate and gene expression of beta cells were analysed in Mafa knockout (KO) mice and mouse models of diabetes in which the expression of MafA was reduced in the majority of beta cells.

Results: Loss of MafA reduced the beta to alpha cell ratio in pancreatic islets without elevating blood glucose to diabetic levels. Lineage tracing analyses showed reduced/lost expression of insulin in most beta cells, with a minority of the former beta cells converted to glucagon-expressing cells in Mafa KO mice. The upregulation of genes that are normally repressed in mature beta cells or transcription factors that are transiently expressed in endocrine progenitors was identified in Mafa KO islets as a hallmark of dedifferentiation. The compromised beta cells in db/db and multiple low-dose streptozotocin mice underwent similar dedifferentiation with expression of Mafb, which is expressed in immature beta cells.

Conclusions/interpretation: The maturation factor MafA is critical for the homeostasis of mature beta cells and regulates cell plasticity. The loss of MafA in beta cells leads to a deeper loss of cell identity, which is implicated in diabetes pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glucagon-Secreting Cells / metabolism
  • Immunohistochemistry
  • Islets of Langerhans / metabolism
  • Maf Transcription Factors / genetics
  • Maf Transcription Factors / metabolism*
  • Maf Transcription Factors, Large / genetics
  • Maf Transcription Factors, Large / metabolism*
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / metabolism
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Reverse Transcriptase Polymerase Chain Reaction


  • Maf Transcription Factors
  • Maf Transcription Factors, Large
  • MafB Transcription Factor
  • Mafa protein, mouse