Study Shows How Metabolism Shapes Identity and Behavior of HSPCs

Researchers from the Max Planck Institute of Immunobiology and Epigenetics and ETH Zürich have assembled a detailed map illuminating the metabolic and molecular transitions of hematopoietic stem and progenitor cells (HSPCs) as they differentiate, age, or undergo malignant changes. This innovative research was made possible by two low-input techniques, allowing comprehensive analysis with far fewer cells than previously required.

By integrating the collected metabolic data with gene expression profiles, the team created a comprehensive “map” of the cell’s chemical processes and gene activity enabling them to trace how blood stem cells change during different stages of health, aging, and disease. “We could find, for instance, that human stem cells are less metabolically active than their more developed descendants. We find fewer metabolites needed for energy production, building cell parts, and making amino acids. This fits with the fact that stem cells usually stay in a resting state to protect themselves and their capabilities,” says Professor Nina Cabezas-Wallscheid, senior author of the Nature Cell Biology paper. 

One focus of the research was on the nutrient choline, prevalent in healthy stem cells but found to diminish during differentiation, aging, and leukemia. Laboratory supplementation of choline was shown to increase lipid production and foster preservation of youthful, stem-like characteristics. This finding points to the potential for nutritional strategies that may help sustain stem cell function.

The study also tracked significant changes in the lipid composition of blood stem cells, which may alter how the cells sense and interact with their surroundings. “These findings provide new directions for exploring how metabolism not only shapes a cell’s internal machinery but also its interactions with the environment,” says co-corresponding author Jörg Büscher.

Overall, these discoveries present a new, integrated view of how metabolism shapes the identity and behavior of blood stem cells and also establishes a foundation for future efforts to develop therapies aimed at preserving stem cell function during aging or disease.