Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

Blog Article

Summary: Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by here the lack of genome-scale network models.Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells.Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates.The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells.

Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive voyage et cie discount code and primed cells.Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate.: Chandrasekaran et al.use computational modeling, metabolomics, and metabolic inhibitors to discover metabolic differences between various pluripotent stem cell states and infer their impact on stem cell fate decisions.

Keywords: systems biology, stem cell biology, metabolism, genome-scale modeling, pluripotency, histone methylation, naive (ground) state, primed state, cell fate, metabolic network.