Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells

J Diabetes Res. 2017;2017:6726901. doi: 10.1155/2017/6726901. Epub 2017 Feb 28.

Abstract

Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreatic β cell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19. Of note, FoxO1 knockdown or FoxO1 inhibitor significantly upregulated Ngn3 and insulin as well as the markers such as Glut2, Kir6.2, SUR1, and VDCC, which are designated for mature β cells. On the contrary, overexpression of FoxO1 suppressed the induction and reduced expression of these β cell markers. Taken together, these results suggest that FoxO1 may act as a repressor to inhibit cell differentiation in human fetal pancreatic progenitor cells.

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism*
  • Glucose Transporter Type 2 / genetics
  • Glucose Transporter Type 2 / metabolism
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Pancreas / cytology
  • Pancreas / metabolism*
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Stem Cells
  • Sulfonylurea Receptors / genetics
  • Sulfonylurea Receptors / metabolism
  • Up-Regulation

Substances

  • ABCC8 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium Channels
  • Forkhead Box Protein O1
  • Glucose Transporter Type 2
  • Insulin
  • Kir6.2 channel
  • NEUROG3 protein, human
  • Nerve Tissue Proteins
  • Potassium Channels, Inwardly Rectifying
  • Sulfonylurea Receptors