摘要：SummaryHuman 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.Graphical AbstractDisplay OmittedHighlights•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 proliferationCell Biology; Metabolomics; Stem Cell Research
