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New Insights into RSeT Human Stem Cell Metabolism

Research reveals unique metabolic traits of RSeT hESCs and their implications for medicine.

― 6 min read


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Human pluripotent stem cells (hPSCs) are special cells that can turn into many different cell types in the body. Over the last twenty years, scientists have discovered different types of these stem cells, specifically in terms of how they develop and function. The main types are called naïve, formative, and primed Pluripotency.

Naïve cells represent the early stage of development before implantation in an embryo, while primed cells are found after the embryo has implanted. The formative state falls between these two. Understanding these different states of pluripotency helps scientists learn about human embryonic development and can lead to advancements in medical treatments.

The Role of Metabolism in Stem Cells

Metabolism refers to the chemical processes in the body that convert food into energy. It is essential for the growth and functioning of all cells, including hPSCs. These stem cells rely on different metabolic processes depending on their state.

Primed cells primarily use a process called glycolysis for energy, which breaks down sugar without needing much oxygen. In contrast, naïve cells use a combination of glycolysis and oxidative phosphorylation, a different process that generates energy using oxygen. Understanding how these different types of stem cells use metabolism can help scientists improve their growth conditions and develop new treatments for diseases.

Research on RSeT hESCs

Recently, researchers have been focusing on a specific medium called RSeT to grow a type of hPSC known as RSeT hESCs. These cells show some unique characteristics that set them apart from other types of stem cells. Although various methods to create hPSCs exist, the growth and behavior of RSeT cells under different conditions have not been fully explored until now.

To gain insight into these cells, researchers examined their metabolism by studying which genes were active, analyzing the molecules present in the cells, and conducting several tests to understand their functions.

Discovering Metabolic Changes in RSeT hESCs

In the investigation, researchers aimed to understand how RSeT cells behave metabolically, especially under different oxygen levels. They found that these cells have metabolic features that differ significantly from primed and naïve hPSCs. For example, they observed changes in how RSeT cells use glucose and other nutrients.

One of the key findings was that RSeT hESCs show a blend of metabolic patterns, which includes the use of fatty acids alongside glycolysis. This indicates that RSeT cells have a more complex metabolism, enabling them to thrive despite varying environmental conditions.

Metabolic Gene Expression Patterns in RSeT hESCs

Researchers conducted an extensive analysis of the genes linked to metabolism in RSeT hESCs. They found specific groups of genes that are more active in these cells, indicating that their metabolic processes are unique.

Among these genes, many are connected to how the body processes fats and sugars. By understanding which metabolic genes are active, researchers can better understand how RSeT cells manage their energy needs and how this might influence their growth and development.

The Impact of Oxygen Levels on Metabolism

Another area of focus was how oxygen levels affect RSeT hESCs. Scientists compared how these cells behave in low oxygen (hypoxia) and normal oxygen (normoxia) conditions. They discovered that the changes in metabolism due to different oxygen levels were less significant than the differences between primed and RSeT states.

This finding suggests that RSeT hESCs can maintain their metabolic processes effectively, regardless of whether they are in low or normal oxygen environments. This adaptability is a crucial factor for their use in research and therapy.

Glycolysis and Oxidative Phosphorylation in RSeT hESCs

The researchers found that while RSeT hESCs still process glucose, they do not do so in the same way naïve cells do. Instead of relying heavily on glycolysis like primed cells, RSeT hESCs maintain a balance between glycolysis and fatty acid oxidation. This balance allows them to generate energy efficiently while also utilizing different sources of nutrients.

Furthermore, the experiments showed that RSeT hESCs had a distinct way of managing by-products from glucose metabolism, indicating that they don't depend solely on glucose during energy production.

Functional Tests to Assess Metabolism

To confirm their findings, the researchers conducted functional tests using specialized equipment to measure how RSeT hESCs use glucose and generate energy. This involved using a method to track acid levels in the cells to evaluate their glycolysis capacity.

Results showed that while RSeT hESCs have a stable glycolytic function, they also possess an elevated capacity for other energy-generating processes, such as oxidative phosphorylation. This means they can adjust their energy production methods depending on the situation.

The Role of Lipid Metabolism

Lipid metabolism, which involves the processing of fats, emerged as a crucial factor in RSeT hESCs. Researchers noticed that these cells have distinct behaviors regarding how they handle fats compared to other types of stem cells.

The study indicated that RSeT hESCs actively engage in breaking down fatty acids for energy, which is less common in traditional stem cell growth. This unique reliance on lipid metabolism may help RSeT cells maintain their pluripotent state while also adapting to various growth conditions.

Differences Among RSeT Cell Lines

Different RSeT hESC lines showed variations in their metabolic profiles. For example, certain lines demonstrated stronger reliance on lipid metabolism, while others showed differences in how they managed energy and nutrient availability.

This variability suggests that each cell line may have its specific metabolic requirements that influence its growth and development. Understanding these differences is essential for optimizing conditions to enhance stem cell production and application.

Understanding Nucleotide Metabolism

Researchers also examined how RSeT hESCs manage their nucleotide metabolism, which is crucial for making DNA and RNA. They discovered that RSeT hESCs exhibit unusual patterns of nucleotide processing compared to other stem cell types.

Notably, certain nucleotide levels were lower in RSeT hESCs, indicating potential shifts in how these cells utilize nucleotides for growth and replication. This finding could explain some of the challenges in promoting cell division in RSeT hESCs.

Implications for Stem Cell Research

The insights gained from studying RSeT hESCs shed light on the complex interplay between a stem cell's metabolic state and its pluripotency. Understanding how metabolic changes influence cell behavior can help researchers improve methods for generating and maintaining stem cells.

Furthermore, these findings have important implications for regenerative medicine and drug development. By refining the conditions under which hPSCs are grown, scientists can enhance their ability to differentiate into specific cell types needed for treatment.

Conclusion

Research on RSeT hESCs has opened up new avenues for understanding stem cell metabolism and pluripotency. The unique metabolic features of these cells highlight the importance of tailoring growth conditions to their specific needs.

As scientists continue to unravel the complexities of stem cell metabolism, it is expected that new strategies will emerge for harnessing the potential of hPSCs in medical applications. Improved knowledge of the relationship between metabolism and stem cell behavior can lead to significant breakthroughs in regenerative medicine and therapeutic development.

Understanding these processes not only enhances our insights into basic biology but also paves the way for innovative treatments that could transform healthcare in the future.

Original Source

Title: Metabolic Quadrivalency in RSeT Human Embryonic Stem Cells

Abstract: One of the most important properties of human embryonic stem cells (hESCs) is related to their pluripotent states. In our recent study, we identified a previously unrecognized pluripotent state induced by RSeT medium. This state makes primed hESCs resistant to conversion to naive pluripotent state. In this study, we have further characterized the metabolic features in these RSeT hESCs, including metabolic gene expression, metabolomic analysis, and various functional assays. The commonly reported metabolic modes include glycolysis or both glycolysis and oxidative phosphorylation (i.e., metabolic bivalency) in pluripotent stem cells. However, besides the presence of metabolic bivalency, RSeT hESCs exhibited a unique metabolome with additional fatty acid oxidation and imbalanced nucleotide metabolism. This metabolic quadrivalency is linked to hESC growth independent of oxygen tension and restricted capacity for naive reprogramming in these cells. Thus, this study provides new insights into pluripotent state transitions and metabolic stress-associated hPSC growth in vitro.

Authors: Kevin G. Chen, K. Park, D. Maric, K. R. Johnson, P. G. Robey, B. S. Mallon

Last Update: 2024-02-22 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.02.21.581486

Source PDF: https://www.biorxiv.org/content/10.1101/2024.02.21.581486.full.pdf

Licence: https://creativecommons.org/publicdomain/zero/1.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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