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PNAS: Donor-dependent variation in hepatic differentiation from human iPS cells

Hepatocytes generated from human induced pluripotent stem cells (iPS cells) constitute an unprecedented resource in the field of drug discovery and cell therapy, but the successful generation of mature hepatocytes from human iPS cells remains a challenge. In studies to identify which types of human iPS cell clone have a high propensity to differentiate into hepatocytes, researchers at the Center for iPS Cell Research and Application (CiRA) at Japan's Kyoto University have found that hepatic differentiation from human iPS cells depends on the identity of the donor of the somatic cells used to produce the iPS cells.

The research group led by CiRA director Professor Shinya Yamanaka and principal investigator Professor Takashi Aoi and Researcher Masatoshi Kajiwara developed an improved method of differentiating hepatic cells from human iPS cell lines. A comparison of 28 human iPS cell lines derived from various types of somatic cell using retroviruses, Sendai viruses, or episomal plasmids suggested that the somatic cell type may influence hepatic differentiation. Human iPS cell clones derived from peripheral blood cells consistently showed good differentiation efficiency, whereas many human iPS cell clones derived from adult skin cells showed poor differentiation.

However, when the researchers compared human iPS cells from the same individual but derived separately from peripheral blood cells and adult skin cells, they found that the variations in hepatic differentiation were mainly attributable to differences in the identity of the donor rather than in the original cell type.

''We have yet to find out which types of iPS cell line differentiate most efficiently into hepatic cells. Our findings underscore the need for researchers to consider the importance of donor differences when comparing the differentiation propensities of human iPS cell clones.'' said Aoi.


Title
"Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells"

Journal
Proceedings of the National Academy of Science


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