An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population

An innovative experimental framework utilizing human induced pluripotent stem cells (hiPSCs) has been developed to study phenotypic variations associated with Jomon ancestry in the present-day Japanese population. Ancestry-related genomic differences may contribute to diverse physical traits, but their cellular implications are challenging to assess.

To tackle this issue, researchers created a hiPSC-based model using the Japanese population as a case study for Jomon-related and continental East Asian ancestry mixing. By measuring Jomon ancestry through the Jomon allele score (JAS), the study found correlations between JAS and clinical parameters, such as renal-related traits and serum triglycerides, in 34,152 participants from the Tohoku Medical Megabank.

Peripheral blood mononuclear cells from donors at both ends of the JAS spectrum (n = 10) exhibited differences in immune-related gene expression. To investigate whether the association between JAS and serum triglycerides extended to hepatic cellular phenotypes, researchers differentiated hiPSCs from these donors into hepatocyte-like cells.

The study discovered that intracellular triglyceride levels and lipid-related gene expression remained unchanged between the two groups. This research underscores the importance of a genetically characterized hiPSC-based framework for examining ancestry-associated phenotypes across various cellular contexts.