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Barcelona BioMed Seminar: Transcriptional regulation by the orphan nuclear receptor NR5A2 links cell differentiation with inflammation in the pancreas


Tissue-specific differentiation and inflammatory programmes are thought to independently contribute to disease. The orphan nuclear receptor NR5A2 is a key regulator of pancreas differentiation and SNPs in or near the human gene are associated with risk of pancreatic cancer. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage and cooperates with mutant KRas in tumor progression. Through global transcriptomic analysis, we uncover a basal pre-inflammatory state in the pancreas of Nr5a2 heterozygous mice that is reminiscent of pancreatitis-induced inflammation: Nr5a2 undergoes a dramatic transcriptional switch relocating from tissue-specific to inflammatory loci thereby promoting AP-1-dependent gene transcription. Deletion of c-Jun in the pancreas of Nr5a2 heterozygous mice rescues the pre-inflammatory phenotype. These findings provide compelling evidence that the same transcriptional networks supporting homeostasis in normal tissue can be subverted to foster inflammation upon genetic or environmental constraints.

Plenary Seminar

Data i hora d'inici: 27/01/2017, 12.00h

Data i hora de fi: 27/01/2017, 14.00h

Organitzador: IRB- Institut de Recerca Biomèdica

Lloc: Edifici Clúster Laboratoris, Aula Félix Serratosa

Host: Dr.Eduard Batlle, IRB Barcelona