HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion

Biochem Biophys Res Commun. 2007 Apr 6;355(2):331-7. doi: 10.1016/j.bbrc.2007.01.153. Epub 2007 Feb 5.


To examine the mechanism by which growth-stimulated pancreatic beta-cells dedifferentiate, somatic cell fusions were performed between MIN6, a highly differentiated mouse insulinoma, and betalox5, a cell line derived from human beta-cells which progressively dedifferentiated in culture. MIN6/betalox5 somatic cells hybrids underwent silencing of insulin expression and a marked decline in PDX1, NeuroD, and MafA, indicating that betalox5 expresses a dominant transacting factor(s) that represses beta-cell differentiation. Expression of Hes1, which inhibits endocrine differentiation was higher in hybrid cells than in parental MIN6 cells. Hes6, a repressor of Hes1, was highly expressed in primary beta-cells as well as MIN6, but was repressed in hybrids. Hes6 overexpression using a retroviral vector led to a decrease in Hes1 levels, an increase in beta-cell transcription factors and partial restoration of insulin expression. We conclude that the balance of Notch activators and inhibitors may play an important role in maintaining the beta-cell differentiated state.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Fusion*
  • Cell Line
  • Cell Nucleus / metabolism*
  • Homeodomain Proteins / metabolism
  • Humans
  • Hybrid Cells
  • Insulin / biosynthesis*
  • Islets of Langerhans / metabolism*
  • Mice
  • Polymerase Chain Reaction
  • Repressor Proteins / physiology*
  • Trans-Activators / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • HES6 protein, human
  • Homeodomain Proteins
  • Insulin
  • Repressor Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein