Abstract
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.
Highlights
Human pluripotent stem cells, including human embryonic stem cells and human induced pluripotent stem cells, have the capacity to differentiate into various cell types, making them a promising cell source for regenerative therapy and drug discovery
Metabolism plays a key role in the maintenance of pluripotency and cell survival of Human pluripotent stem cells (hPSCs) (Carey et al, 2015; Folmes et al, 2011; Marsboom et al, 2016; Moussaieff et al, 2015; Shiraki et al, 2014; Teslaa et al, 2016; Tohyama et al, 2013, 2016; Vardhana et al, 2019; Wang et al, 2009). hPSCs depend on activated glycolysis and glutamine metabolism for production of ATP, as well as biomass for maintenance of pluripotency and cell survival
TRP supplementation promotes proliferative capacity in human induced pluripotent stem cells (hiPSCs) Consumption of amino acid (AA) in hiPSCs in mTeSR1 maintenance medium over 3 days was first measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Summary
Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), have the capacity to differentiate into various cell types, making them a promising cell source for regenerative therapy and drug discovery. Metabolism plays a key role in the maintenance of pluripotency and cell survival of hPSCs (Carey et al, 2015; Folmes et al, 2011; Marsboom et al, 2016; Moussaieff et al, 2015; Shiraki et al, 2014; Teslaa et al, 2016; Tohyama et al, 2013, 2016; Vardhana et al, 2019; Wang et al, 2009). Understanding the unique metabolism of hPSCs could lead to development of a method for efficient differentiation and elimination of residual undifferentiated stem cells (Marsboom et al, 2016; Shiraki et al, 2014; Tanosaki et al, 2020; Tohyama et al, 2013, 2016; Yanes et al, 2010). Little is known about optimal concentrations for each amino acid (AA) and the relationship between AA metabolism and proliferation in hPSCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
