Human stem cell models: lessons for pancreatic development and disease

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 inter...

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Bibliographic Details
Published in:Genes & development 2019-11, Vol.33 (21-22), p.1475-1490
Main Authors: Gaertner, Bjoern, Carrano, Andrea C, Sander, Maike
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.331397.119