title: Deletion of retinoic acid receptor β (RARβ) impairs pancreatic endocrine differentiation.
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.
authors.affiliation: Pharmacology Department, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Pérez
authors.forename: Yannick D
authors.initials: YD
authors.lastname: Benoit
authors.forename: Lorraine J
authors.initials: LJ
authors.lastname: Gudas
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D018168:Receptors, Retinoic Acid; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C082925:retinoic acid receptor beta; D014212:Tretinoin; D005934:Glucagon
keywords: ES; Endocrine; Gcg; Iapp; Ins1; Islet cells; KO; Neurogenin3; Ngn3; Pancreas; RA; RAR; RARE; RARβ; Retinoic acid; Sst; Stem cell; WT; all-trans retinoic acid; embryonic stem; glucagon; insulin 1; islet amyloid polypeptide; knockout; retinoic acid receptor; retinoic acid response element; somatostatin; wild-type