Folate-mediated one carbon metabolism is essential for de novo nucleotide synthesis, cellular methylation, regulation of mitochondrial metabolism. These processes are critical to the maintenance and development of hematopoietic stem cells (HSCs). HSCs are generated during fetal development and are responsible for generation of all blood cells across the lifespan. Universal folic acid supplementation of the population is currently utilized for the prevention of common birth defects, but there are currently no known studies on the influence of prenatal folic acid supplementation on the development of HSCs. To examine the effects of prenatal folic acid supplementation on HSC function, wild type C57BL/6 female mice were weaned onto one of three diets, 0mg/kg (folate deficient, FD), 2mg/kg (folate control, FC), or 8mg/kg (folate supplemented, FS), and mice were timed mated to generate litters under each condition. Both FD and FS significantly decreased fetal weights at embryonic day (E)14.5 as compared to FC offspring. Despite growth restriction, profiling of the developing hematopoietic compartment using flow cytometry at E14.5 revealed overall expansion of all blood cells in response to FD as compared to FC offspring, whereas all blood cells were significantly reduced in FS offspring. Increased blood cells in FD offspring were driven by expansion of HSCs and all downstream progenitor and mature cells. In contrast, FS caused decreased mature myeloid and lymphoid cells at E14.5, whereas hematopoietic stem and progenitor cells (HSPCs) were unaffected. To determine the underlying mechanisms of varying prenatal folate on hematopoietic output, we metabolically profiled E14.5 HSPCs to determine OXPHOS (oxidative phosphorylation) and glycolytic activity. Preliminary results show that FS offspring exhibited higher rates of glycolytic activity as compared to FC offspring. Additionally, FS offspring had higher OXPHOS activity per cell as compared to FC offspring. These data reveal that prenatal folate alters HSPC metabolism during fetal life.
University / Institution: University of Utah
Format: In Person
SESSION D (3:30-5:00PM)
Area of Research: Health & Medicine
Faculty Mentor: Anna Beaudin