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provided the spheroids and instructed on the spheroids culture methods. K.K., K.O., and
Y.S. provided the human colorectal cancer specimens. S.K. supervised the study. T. Ito
and S.K. wrote the manuscript.
Competing interests
S.K. is a founder, shareholder, and chief scientific officer at Thyas Co., Ltd. and received
research funding from Thyas Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kirin Co., Ltd.,
TERUMO Co., Ltd., Astellas Pharma Co., Ltd. and Tosoh Co. Ltd. The remaining
authors declare no competing interests.
Additional information
Supplementary information The online version contains supplementary material
available at https://doi.org/10.1038/s42003-021-02195-x.
Correspondence and requests for materials should be addressed to S.K.
Acknowledgements
Reprints and permission information is available at http://www.nature.com/reprints
We thank Shinya Yamanaka for providing critical advice; Takehito Yamamoto for
providing the spheroids; Kanae Mitsunaga for technical assistance with the flow cytometry analysis; Shunsuke Kihara for technical assistance with the time-lapse imaging;
Yoriko Indo, Daisuke Seki and Akito Tanaka for supporting the animal experiments;
Norikazu Saiki, Kohei Ohara, Eri Imai, Kaede Makino, Sanae Kamibayashi, Munehiro
Yoshida, Kengo Nakagoshi, Shuichi Kitayama, Tadayo Miyasaka, Sayaka Okamoto,
Ayako Kumagai, Yoshihiro Iwamoto, Yoshitaka Ishiguro, Masahiro Tanaka, Tatsuki
Ueda, Masazumi Waseda, Akihiro Ishikawa, Bo Wang, Sara Shiina, Reiko Saikawa, Yuta
Mishima, Hitomi Takakubo, Yukie Seto, and Katsura Noda for technical assistance; and
Peter Karagiannis for editing the manuscript. This study was supported in part by a
Grant-in-Aid for Scientific Research (KAKENHI) and collaborative research grant of
Thyas Co., Ltd.
Author contributions
T. Ito and S.K. designed the concept and study. T. Ito performed the experiments and
acquired the data. Y.Y. cooperated with the iPSC establishment from TIL. T. Ito and S.K.
analyzed and interpreted the data. Y.K., S.I., and A.M. provided protocols and advice for
the experiments. T. Ishii cooperated with the in vivo experiments. H.M. and M.M.T.
16
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