Metabolic Programming of Hematopoietic Stem Cell Function by Prenatal Folate

Hematopoietic stem cells (HSCs) arise during fetal development and give rise to all blood and immune cells throughout the entire lifespan. This project explores how prenatal folate status shapes the establishment and function of HSCs. Folate, a key nutrient involved in cellular methylation and epigenetic regulation as well as mitochondrial metabolism, is critical for maintaining HSC function. Additionally, folate deficiency is linked to neural tube defects, which is prevented in many countries by fortification of folic acid.

Our data suggests that manipulation of prenatal folate alters offspring HSC function and self-renewal through underlying epigenetic and metabolic programs. This project utilizes metabolic assays, stem cell transplantation, hematopoietic profiling and multiomics approaches to understand all aspects of prenatal folate programming. We now seek to understanding the underlying mechanisms of prenatal folate- mediated metabolic programming of offspring HSC function.