Deletion of retinoic acid receptor β (RARβ) impairs pancreatic endocrine differentiation.

TitleDeletion of retinoic acid receptor β (RARβ) impairs pancreatic endocrine differentiation.
Publication TypeJournal Article
Year of Publication2013
AuthorsPérez RJ, Benoit YD, Gudas LJ
JournalExp Cell Res
Volume319
Issue14
Pagination2196-204
Date Published2013 Aug 15
ISSN1090-2422
KeywordsAnimals, Cell Differentiation, Cell Line, Embryonic Stem Cells, Gene Deletion, Gene Expression Regulation, Developmental, Glucagon, Homeodomain Proteins, Insulin, Islet Amyloid Polypeptide, Islets of Langerhans, Mice, Mice, Inbred C57BL, Receptors, Retinoic Acid, Trans-Activators, Transcription, Genetic, Tretinoin
Abstract

All-trans retinoic acid (RA) signals via binding to retinoic acid receptors (RARs α, β, and γ). RA directly influences expression of Pdx1, a transcription factor essential for pancreatic development and beta-cell (β-cell) maturation. In this study we follow the differentiation of cultured wild-type (WT) vs. RARβ knockout (KO) embryonic stem (ES) cells into pancreatic islet cells. We found that RARβ KO ES cells show greatly reduced expression of some important endocrine markers of differentiated islet cells, such as glucagon, islet amyloid polypeptide (Iapp), and insulin 1 (Ins1) relative to WT. We conclude that RARβ activity is essential for proper differentiation of ES cells to pancreatic endocrine cells.

DOI10.1016/j.yexcr.2013.05.032
Alternate JournalExp. Cell Res.
PubMed ID23756134
PubMed Central IDPMC3821387
Grant ListT32 CA062948 / CA / NCI NIH HHS / United States
T32DK07313 / DK / NIDDK NIH HHS / United States
R01CA043796 / CA / NCI NIH HHS / United States
T32 DK007313 / DK / NIDDK NIH HHS / United States
R01 CA043796 / CA / NCI NIH HHS / United States