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Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells.

iScience (2021-02-23)
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
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Serine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Methionine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 99.0-101.0%
Sigma-Aldrich
L-Arginine monohydrochloride, not synthetic, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Tryptophan, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 99.0-101.0%
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
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L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
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L-Glutamic acid, from non-animal source, meets EP testing specifications, suitable for cell culture, 98.5-100.5%
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L-Isoleucine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
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L-Phenylalanine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
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L-Ascorbic acid, BioXtra, ≥99.0%, crystalline
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
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L-Proline, from non-animal source, meets EP, USP testing specifications, suitable for cell culture
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L-Cysteine hydrochloride monohydrate, from non-animal source, suitable for cell culture, meets EP, USP testing specifications
Sigma-Aldrich
L-Threonine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 99.0-101.0%
Sigma-Aldrich
L-Alanine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Leucine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
Ro 61-8048, ≥98% (HPLC)