Human stem cell models: lessons for pancreatic development and disease

Genes Dev. 2019 Nov 1;33(21-22):1475-1490. doi: 10.1101/gad.331397.119.

Abstract

A comprehensive understanding of mechanisms that underlie the development and function of human cells requires human cell models. For the pancreatic lineage, protocols have been developed to differentiate human pluripotent stem cells (hPSCs) into pancreatic endocrine and exocrine cells through intermediates resembling in vivo development. In recent years, this differentiation system has been employed to decipher mechanisms of pancreatic development, congenital defects of the pancreas, as well as genetic forms of diabetes and exocrine diseases. In this review, we summarize recent insights gained from studies of pancreatic hPSC models. We discuss how genome-scale analyses of the differentiation system have helped elucidate roles of chromatin state, transcription factors, and noncoding RNAs in pancreatic development and how the analysis of cells with disease-relevant mutations has provided insight into the molecular underpinnings of genetically determined diseases of the pancreas.

Keywords: embryonic; pancreatic development; stem cell.

Publication types

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

MeSH terms

  • Cell Differentiation
  • Genome-Wide Association Study
  • Humans
  • Models, Biological*
  • Pancreas / cytology*
  • Pancreas / growth & development*
  • Pancreas / pathology
  • Pancreatic Diseases / genetics
  • Pancreatic Diseases / physiopathology
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / physiology