Maternal Folate Nutrition Programs Adult Hematopoietic Stem Cell Function Through Mitochondrial Remodeling

Maternal folate availability in mice programs adult hematopoietic stem cell function in a dose-dependent manner, with deficiency impairing self-renewal and supplementation enhancing it.

• Why it matters: Folate-dependent one-carbon metabolism may regulate HSC programming during development, but broader consequences of maternal folate status for the hematopoietic system remain poorly defined.
• What they did: Using dietary models of maternal folate deficiency or supplementation in mice, the study assessed adult offspring HSC self-renewal alongside mitochondrial, chromatin, and fetal HSC metabolomics readouts.
• The result: Folate deficiency impaired adult HSC self-renewal with mitochondrial defects, elevated proteotoxic stress, and a stress-adapted chromatin landscape, while supplementation improved mitochondrial quality control, CDC42-associated organelle remodeling, and chromatin permissive for maintenance.