Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells.
Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells.
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DOI：
10.1016/j.isci.2021.102090
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Fukuda K
中科院分区：
文献类型：
--
作者：
Someya S;Tohyama S;Kameda K;Tanosaki S;Morita Y;Sasaki K;Kang MI;Kishino Y;Okada M;Tani H;Soma Y;Nakajima K;Umei T;Sekine O;Moriwaki T;Kanazawa H;Kobayashi E;Fujita J;Fukuda K
人类多能干细胞（hPSC）具有独特的代谢特征，用于维持多能性、自我更新和存活。虽然hPSC可潜在地用于再生医学，但与大规模细胞培养相关的高昂成本对hPSC的临床应用提出了主要障碍。此外，在没有完全表征的代谢特征的情况下，hPSC培养条件没有优化。在这里，我们进行了详细的氨基酸分析，发现色氨酸（TRP）在维持多能性的增殖中起着关键作用。此外，代谢组学分析显示，在TRP补充条件下，细胞内和细胞外犬尿氨酸（KYN）减少，而KYN的上游代谢物N-甲酰犬尿氨酸（NFK）增加，从而促进增殖。总之，我们证明TRP对于hPSC的存活和增殖是不可或缺的。对TRP代谢的深入了解将使hPSC的大规模生产具有成本效益，从而推动再生医学的发展。TRP是唯一的AA，其能够通过补充来增强hPSC增殖。在TRP补充中长期培养后，hPSC以多能性增殖。hPSC的增殖特性不依赖于AhR信号传导。TRP衍生的NFK有助于增强hPSC增殖。
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. TRP is the only AA that enables enhanced hPSC proliferation by supplementation hPSCs proliferate with pluripotency after long-term culture in TRP supplementation The proliferative properties of hPSCs are independent of AhR signaling TRP-derived NFK contributes to enhanced hPSC proliferation Cell Biology; Metabolomics; Stem Cell Research
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影响因子：
29
作者：
TeSlaa T;Chaikovsky AC;Lipchina I;Escobar SL;Hochedlinger K;Huang J;Graeber TG;Braas D;Teitell MA
通讯作者：
Teitell MA
影响因子：
7.4
作者：
Soga, T;Heiger, DN
通讯作者：
Heiger, DN
色氨酸衍生物调节干细胞样癌细胞中 Oct4 的转录。
影响因子：
16.6
作者：
Cheng, Jie;Li, Wenxin;Kang, Bo;Zhou, Yanwen;Song, Jiasheng;Dan, Songsong;Yang, Ying;Zhang, Xiaoqian;Li, Jingchao;Yin, Shengyong;Cao, Hongcui;Yao, Hangping;Zhu, Chenggang;Yi, Wen;Zhao, Qingwei;Xu, Xiaowei;Zheng, Min;Zheng, Shusen;Li, Lanjuan;Shen, Binghui;Wang, Ying-Jie
通讯作者：
Wang, Ying-Jie
影响因子：
5.9
作者：
Tohyama S;Fujita J;Fujita C;Yamaguchi M;Kanaami S;Ohno R;Sakamoto K;Kodama M;Kurokawa J;Kanazawa H;Seki T;Kishino Y;Okada M;Nakajima K;Tanosaki S;Someya S;Hirano A;Kawaguchi S;Kobayashi E;Fukuda K
通讯作者：
Fukuda K
影响因子：
5.8
作者：
Tanosaki S;Tohyama S;Fujita J;Someya S;Hishiki T;Matsuura T;Nakanishi H;Ohto-Nakanishi T;Akiyama T;Morita Y;Kishino Y;Okada M;Tani H;Soma Y;Nakajima K;Kanazawa H;Sugimoto M;Ko MSH;Suematsu M;Fukuda K
通讯作者：
Fukuda K