De novo formation of insulin-producing "neo-β cell islets" from intestinal crypts. Academic Article uri icon

Overview

abstract

  • The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell "reprogramming factors" in a wide spectrum of tissues. We report that transient intestinal expression of these factors-Pdx1, MafA, and Ngn3 (PMN)-promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into "neoislets" below the crypt base. Neoislet cells express insulin and show ultrastructural features of β cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal "organoids" stimulates the conversion of intestinal epithelial cells into β-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.

publication date

  • March 6, 2014

Research

keywords

  • Insulin
  • Insulin-Secreting Cells
  • Intestines
  • Islets of Langerhans

Identity

PubMed Central ID

  • PMC4245054

Scopus Document Identifier

  • 84897030116

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2014.02.013

PubMed ID

  • 24613355

Additional Document Info

volume

  • 6

issue

  • 6