“Remember to take your vitamins!” This colloquial phrase is commonly used to encourage multivitamin use. Beyond preventing neural tube defects, there may be a new reason to make sure pregnant people get their daily dose of folate. Brian Krum, MSc, presented the abstract “Metabolic Programming of Hematopoietic Stem Cell Function by Prenatal Folate” yesterday at the Plenary Scientific Session. Mr. Krum is a graduate student in the lab of Anna Beaudin, PhD, at the University of Utah, Division of Hematology, and Huntsman Cancer Institute. Dr. Beaudin has had an interest in stem cell biology since early in her career. “Hematopoietic stem cell biology is the ‘ultimate’ stem cell system because it's still the only stem cell that you can isolate to single-cell purity and use to reconstitute an entire organ system,” she said. “I always found that to be absolutely fascinating.”
The superb presentation described the team’s work in understanding the impact of prenatal folate status on metabolic changes and hematopoietic stem cell function. They varied folate consumption to study the effects of prenatal folate deficiency and supplementation compared to controls. They found variations in fetal liver stem cell output that appeared to be driven by metabolic changes related to prenatal folate intake. Through a series of experiments in their murine model, Mr. Krum and colleagues demonstrated that adult hematopoietic stem cell output is influenced by prenatal folate exposure, with folate-supplemented offspring having increased hematopoietic progenitors and mature cells and improved engraftment in transplantation studies compared to folate-deficient offspring. They also demonstrated distinct clustering in single-cell RNA sequencing of hematopoietic stem cells from folate-deficient and folate-supplemented offspring compared to control. There were also signs of mitochondrial dysfunction on metabolomic profiling that was present in folate deficient offspring’s hematopoietic stem cells and later stage lymphoid-biased multipotent progenitors, indicating that metabolic pathways are involved in hematopoiesis in a folate-deficient model. These changes were not seen in folate-supplemented mice. The authors conclude that this indicates hematopoietic stem cell metabolic programming is dependent on the dose of fetal folate exposure and that this effect on hematopoietic stem cell function persists into adulthood.
The work of Mr. Krum and colleagues demonstrates a new role for folate in hematopoiesis, with ongoing effects on hematopoietic stem cells into adulthood. These findings may help unravel some of the mysteries around metabolic programming in hematopoiesis. The team is interested in understanding the implications of this work on cancer risk and improving cancer treatments. Dr. Beaudin acknowledged her collaborators: “Brian and I are lucky to be able to partner with great people to support the questions we want to address and constantly learn from others. That's the joy of doing science.”
