PubMed · 42213079
Genomics-informed approach identifies which cell types regulate the metabolome.
Abstract
MOTIVATION: Metabolism occurs in a cell type-specific manner, but which cells regulate metabolite levels remains unclear. RESULTS: Here, we integrate some of the largest metabolite quantitative trait loci datasets, TOPMed and UK Biobank, with one of the most extensive single-cell RNA sequencing resources, Tabula Sapiens. This integration allows us to identify cell types that regulate metabolites body-wide. We find hepatocytes are the primary regulatory cell type for most metabolites, associating with 385/410 (94%) metabolites for whom an association is found. Additionally, our multi-gene approach reveals more metabolite associations with beta cells compared to those identified using a single-gene approach. For example, we identify novel metabolite-cell type associations, such as the association between phenylpropanoic acid and beta cells, this metabolite that was previously thought to be regulated by the microbiome. AVAILABILITY: Code used in this work is available via Github at https://github.com/haimkru/Metabolite-Cell-Type-Associations.
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Haim Krupkin, Evin M Padhi, Daniel Nachun, Jessica Kain, Jonathan Z Long, Stephen B Montgomery. 2026-06-01. Genomics-informed approach identifies which cell types regulate the metabolome.. https://doi.org/10.1093/bioinformatics%2Fbtag330
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