GEO series

Vitamin B2 Sensing by the Nuclear Receptor AhR Reprograms Hepatic Metabolism [RNA-Seq]

GSE341321 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 100 samples Submitted 2026/08/01 Platform GPL34290Platform GPL34284Platform GPL30173

Summary

Nuclear receptors such as RAR/RXR and VDR directly sense vitamins A and D, but analogous sensing mechanisms for most other vitamins remain unknown. Here we identify a metabolite sensing pathway linking vitamin B2 (riboflavin) availability to an adaptive gene expression program. Riboflavin deficiency limits the FAD-dependent enzyme kynurenine 3-monooxygenase, leading to accumulation of kynurenine, an endogenous ligand of the aryl hydrocarbon receptor (AhR). Kynurenine-induced AhR nuclear translocation selectively activates poised hepatic enhancers in cooperation with AP-1 and C/EBPα, inducing glucuronidation genes and the FAD synthase gene FLAD1. This response is required to maintain intracellular FAD levels and support cell fitness under riboflavin-limiting conditions. In vivo, dietary riboflavin deficiency enhances hepatic drug clearance and reduces irinotecan toxicity. Together, these findings reveal a vitamin-sensing mechanism in which a cofactor-dependent enzyme acts as the sensor and AhR functions as the transcriptional effector that enables both flavin homeostasis and hepatic clearance capacity.

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Direct links to NCBI, no account and no request form: the whole study as GSE341321_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 100 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1501342 and SRA study SRP721052. Searching any of these in the dataset finder brings you back here.

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Study design

13 conditions, mostly in triplicate

HepG2_Day3_Cont_RNA ×3 HepG2_Day3_B2_minus_RNA ×3 HepG2_Day6_Cont_RNA ×3 HepG2_Day6_B2_minus_RNA ×3 HepG2_Day9_Cont_RNA ×3 HepG2_Day9_B2_minus_RNA ×3 HepG2_Day12_Cont_RNA ×3 HepG2_Day12_B2_minus_RNA ×3 +6 more

Supports a between-group comparison across 39 samples.

13 replicated groups read from the first 40 of 100 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.

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