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Effect of Prenatal Folate on HSC Function

Semester: Summer 2023

Presentation description

The developmental origins of disease hypothesis states that risk for adult-onset diseases originates during development and is driven by nutritional intake. Folic acid supplements food to aid in the prevention of neural tube defects and has been shown to modify risk for certain adult-onset diseases, including cardiovascular disease and diabetes. Folate mediated one-carbon metabolism regulates cell processes that are critical for hematopoietic (blood) stem cell (HSC) establishment and function, including cell proliferation, DNA methylation, and mitochondrial metabolism. HSCs arise during fetal development and are responsible for the production of all blood and immune cells across the lifespan (hematopoiesis). We hypothesized that prenatal folate status influences the development of HSCs and drives long-term changes to adult hematopoiesis and hematopoietic function. To test this hypothesis, we determined the effects of prenatal folate status on the ability of adult offspring to respond to cytotoxic hematopoietic challenge. Female mice were weaned onto one of 3 diets to model folate consumption (0mg/kg deficient FD, 2mg/kg control FC, or 8mg/kg supplemented FS). Pregnant females were maintained on folate diets through weaning, after which offspring were weaned onto standard chow. Previous examination of hematopoiesis in the adult bone marrow (BM) of FD or FS offspring indicates that BM HSCs are permanently affected by early folate nutrition. Offspring mice (8-12 weeks) were treated with 150mg/kg of the cytotoxic chemotherapeutic 5-fluorouracil (5-FU) and bled every 7 days until termination. 5-FU inhibits cell proliferation and disrupts RNA and DNA synthesis. Analysis did not reveal any changes of blood cell count across any of the groups. However, the FS adult offspring exhibited moderately increased survival in response to cytotoxic challenge with 5-FU compared to FD and FC. This data is consistent with previous observation of enhanced hematopoietic output from FS adult HSCs. Future studies plan to determine the molecular mechanism of metabolic programming in HSCs.

Presenter Name: Amy Richards
Presentation Type: Poster
Presentation Format: In Person
Presentation #104
College: Medicine
School / Department: Internal Medicine
Research Mentor: Anna Beaudin
Date | Time: Thursday, Aug 3rd | 10:30 AM