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

Masatoshi Kajiwara, Takashi Aoi, Keisuke Okita, Ryosuke Takahashi, Haruhisa Inoue, Naoya Takayama, Hiroshi Endo, Koji Eto, Junya Toguchida, Shinji Uemoto, Shinya Yamanaka

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    175 Scopus citations

    Abstract

    Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. However, the in vitro directed differentiation of human pluripotent stem cells into mature hepatocytes remains challenging. Little attention has so far been paid to variations among hiPSC lines in terms of their hepatic differentiation. In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation. The hiPSC clones derived from peripheral blood cells consistently showed good differentiation efficiency, whereas many hiPSC clones from adult dermal fibroblasts showed poor differentiation. However, when we compared hiPSCs from peripheral blood and dermal fibroblasts from the same individuals, we found that variations in hepatic differentiation were largely attributable to donor differences, rather than to the types of the original cells. These data underscore the importance of donor differences when comparing the differentiation propensities of hiPSC clones.

    Original languageEnglish (US)
    Pages (from-to)12538-12543
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume109
    Issue number31
    DOIs
    StatePublished - Jul 31 2012

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    Keywords

    • DNA methylation
    • Endodermal differentiated hiPSCs
    • Regenerative medicine

    ASJC Scopus subject areas

    • General

    Cite this

    Kajiwara, M., Aoi, T., Okita, K., Takahashi, R., Inoue, H., Takayama, N., Endo, H., Eto, K., Toguchida, J., Uemoto, S., & Yamanaka, S. (2012). Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 109(31), 12538-12543. https://doi.org/10.1073/pnas.1209979109