In vivo reprogramming of adult pancreatic exocrine cells to beta-cells

Nature. 2008 Oct 2;455(7213):627-32. doi: 10.1038/nature07314. Epub 2008 Aug 27.

Abstract

One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / analysis
  • Cell Shape
  • Cell Size
  • Cell Transdifferentiation*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Hyperglycemia / metabolism
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / ultrastructure
  • Maf Transcription Factors, Large / genetics
  • Maf Transcription Factors, Large / metabolism
  • Mice
  • Neovascularization, Physiologic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Pancreas, Exocrine / cytology*
  • Pancreas, Exocrine / embryology
  • Pancreas, Exocrine / metabolism
  • Regenerative Medicine / methods
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Homeodomain Proteins
  • Insulin
  • Maf Transcription Factors, Large
  • Mafa protein, mouse
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein

Associated data

  • GEO/GSE12025