Endothelial cells control pancreatic cell fate at defined stages through EGFL7 signaling. Academic Article uri icon

Overview

MeSH

  • Cell Line
  • Cell Proliferation
  • Coculture Techniques
  • Embryonic Stem Cells
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins
  • Humans
  • Immunophenotyping
  • Phenotype
  • Stem Cell Niche
  • Trans-Activators
  • Transcriptome

MeSH Major

  • Cell Communication
  • Cell Differentiation
  • Endothelial Cells
  • Endothelial Growth Factors
  • Pancreas
  • Signal Transduction

abstract

  • Although endothelial cells have been shown to affect mouse pancreatic development, their precise function in human development remains unclear. Using a coculture system containing human embryonic stem cell (hESC)-derived progenitors and endothelial cells, we found that endothelial cells play a stage-dependent role in pancreatic development, in which they maintain pancreatic progenitor (PP) self-renewal and impair further differentiation into hormone-expressing cells. The mechanistic studies suggest that the endothelial cells act through the secretion of EGFL7. Consistently, endothelial overexpression of EGFL7 in vivo using a transgenic mouse model resulted in an increase of PP proliferation rate and a decrease of differentiation toward endocrine cells. These studies not only identified the role of EGFL7 as the molecular handle involved in the crosstalk between endothelium and pancreatic epithelium, but also provide a paradigm for using hESC stepwise differentiation to dissect the stage-dependent roles of signals controlling organogenesis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • February 10, 2015

has subject area

  • Cell Communication
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Coculture Techniques
  • Embryonic Stem Cells
  • Endothelial Cells
  • Endothelial Growth Factors
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins
  • Humans
  • Immunophenotyping
  • Pancreas
  • Phenotype
  • Signal Transduction
  • Stem Cell Niche
  • Trans-Activators
  • Transcriptome

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4325230

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2014.12.008

PubMed ID

  • 25601205

Additional Document Info

start page

  • 181

end page

  • 189

volume

  • 4

number

  • 2