Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells
Shota Someya,
Shugo Tohyama,
Kotaro Kameda,
Sho Tanosaki,
Yuika Morita,
Kazunori Sasaki,
Moon-Il Kang,
Yoshikazu Kishino,
Marina Okada,
Hidenori Tani,
Yusuke Soma,
Kazuaki Nakajima,
Tomohiko Umei,
Otoya Sekine,
Taijun Moriwaki,
Hideaki Kanazawa,
Eiji Kobayashi,
Jun Fujita,
Keiichi Fukuda
Affiliations
Shota Someya
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Shugo Tohyama
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Department of Organ Fabrication, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Corresponding author
Kotaro Kameda
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Sho Tanosaki
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Yuika Morita
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Kazunori Sasaki
Human Metabolome Technologies, Inc., Tsuruoka, Yamagata 997-0052, Japan
Moon-Il Kang
Human Metabolome Technologies, Inc., Tsuruoka, Yamagata 997-0052, Japan
Yoshikazu Kishino
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Marina Okada
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Hidenori Tani
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Yusuke Soma
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Kazuaki Nakajima
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Tomohiko Umei
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Otoya Sekine
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Taijun Moriwaki
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Hideaki Kanazawa
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Eiji Kobayashi
Department of Organ Fabrication, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Jun Fujita
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Endowed Course for Severe Heart Failure Treatment II, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Corresponding author
Keiichi Fukuda
Department of Cardiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Summary: Human pluripotent stem cells (hPSCs) have a unique metabolic signature for maintenance of pluripotency, self-renewal, and survival. Although hPSCs could be potentially used in regenerative medicine, the prohibitive cost associated with large-scale cell culture presents a major barrier to the clinical application of hPSC. Moreover, without a fully characterized metabolic signature, hPSC culture conditions are not optimized. Here, we performed detailed amino acid profiling and found that tryptophan (TRP) plays a key role in the proliferation with maintenance of pluripotency. In addition, metabolome analyses revealed that intra- and extracellular kynurenine (KYN) is decreased under TRP-supplemented conditions, whereas N-formylkynurenine (NFK), the upstream metabolite of KYN, is increased thereby contributing to proliferation promotion. Taken together, we demonstrate that TRP is indispensable for survival and proliferation of hPSCs. A deeper understanding of TRP metabolism will enable cost-effective large-scale production of hPSCs, leading to advances in regenerative medicine.
