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The aryl hydrocarbon receptor binds to kynurenine and mediates a signal supports the undifferentiated state in pluripotent stem cells

ABSTRACT: Kynurenine is generated from tryptophan by indoleamine 2,3-dioxygenase (IDO1) and binds to the aryl hydrocarbon receptor (AhR). We found that kynurenine generated by human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) stimulated the AhR to bind selectively to the promoters and enhancers of self-renewal genes, thus enhancing their transcription. The kynurenine-AhR complex also directly stimulated the expression of IDO1 and AHR, activating a positive feedback loop. Substantial amounts of kynurenine that were not complexed with AhR were present in the culture medium, providing a paracrine signal for maintenance of the undifferentiated state. Kynurenine was not present in the medium of differentiated ESCs and iPSCs. When cells were induced to undergo ectodermal differentiation, the abundance of kynurenine in the medium was reduced through activation of the main kynurenine catabolic pathway mediated by aminotransferase 2 (KAT2), resulting in the secretion of 2-aminoadipic acid (2-AAA) into the culture medium. Thus, kynurenine in the culture medium is a biomarker for the undifferentiated state, and 2-AAA in the culture medium is a biomarker for ESCs and iPSCs that have committed to differentiate along the ectoderm lineage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129507 | GEO | 2019/06/09

REPOSITORIES: GEO

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The aryl hydrocarbon receptor binds to kynurenine and mediates a signal supports the undifferentiated state in pluripotent stem cells

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