NIH R01 · 2024
The role of ascorbate in myelopoiesis and infection
PROJECT SUMMARY: We have developed methods to profile the metabolome of hematopoietic stem cells (HSCs) and other rare cell types purified from tissues. Each hematopoietic cell type had a distinct metabolite identity. Most metabolites were enriched or depleted in specific cell types, suggesting they may have novel cell-type specific roles. HSCs and multipotent progenitors (MPPs) in mouse and human bone marrow had high levels of ascorbate (Vitamin C), which promoted the activity of the enzyme TET2, a suppressor of HSC function. Hematopoietic-specific ascorbate deficiency promoted HSC function, myelopoiesis and the generation of inflammatory myeloid cells, and caused early lethality.…
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