An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population
- 1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
Abstract
Ancestry-related genomic variation may contribute to phenotypic diversity. However, its cellular consequences remain difficult to evaluate. To address this, we developed a human induced pluripotent stem cell (hiPSC)-based framework for investigating such phenotypes. We used the Japanese population as a model of Jomon-related and continental East Asian ancestry admixture. Jomon ancestry, estimated using the Jomon allele score (JAS), was associated with clinical measures, including renal-related traits and serum triglycerides in 34,152 Tohoku Medical Megabank participants. Peripheral blood mononuclear cell transcriptomics of donors from the upper and lower extremes of the JAS distribution (n = 10) suggested group-level differences in immune-related gene expression. To test whether the serum triglyceride association coincided with hepatic cellular phenotypes, we differentiated hiPSCs from these donors into hepatocyte-like cells. Neither intracellular triglycerides nor lipid-related gene expression differed between groups. These findings highlight the value of a genetically characterized hiPSC-based framework for investigating ancestry-associated phenotypes across cellular contexts.
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BibTeX
@misc{nakamura2026ipscbased,
title = {{An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population}},
author = {Y. Nakamura and Y. Watanabe and H. Tanabe and A. Hirai and K. Higashi and K. Kurokawa and A. Toyoda and T. Kato and M. Tsukahara and K. Koganebuchi and Y. Hamazaki and T. Takebe and M. Imamura and T. Ishida and J. Ohashi and H. Oota},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.756619},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.756619v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population
AU - Y. Nakamura
AU - Y. Watanabe
AU - H. Tanabe
AU - A. Hirai
AU - K. Higashi
AU - K. Kurokawa
AU - A. Toyoda
AU - T. Kato
AU - M. Tsukahara
AU - K. Koganebuchi
AU - Y. Hamazaki
AU - T. Takebe
AU - M. Imamura
AU - T. Ishida
AU - J. Ohashi
AU - H. Oota
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.756619
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.756619v1
AB - Ancestry-related genomic variation may contribute to phenotypic diversity. However, its cellular consequences remain difficult to evaluate. To address this, we developed a human induced pluripotent stem cell (hiPSC)-based framework for investigating such phenotypes. We used the Japanese population as a model of Jomon-related and continental East Asian ancestry admixture. Jomon ancestry, estimated using the Jomon allele score (JAS), was associated with clinical measures, including renal-related traits and serum triglycerides in 34,152 Tohoku Medical Megabank participants. Peripheral blood mononuclear cell transcriptomics of donors from the upper and lower extremes of the JAS distribution (n = 10) suggested group-level differences in immune-related gene expression. To test whether the serum triglyceride association coincided with hepatic cellular phenotypes, we differentiated hiPSCs from these donors into hepatocyte-like cells. Neither intracellular triglycerides nor lipid-related gene expression differed between groups. These findings highlight the value of a genetically characterized hiPSC-based framework for investigating ancestry-associated phenotypes across cellular contexts.
ER -