NAD⁺ supplementation has significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevating NAD⁺ to physiological levels has been shown to improve the function of some adult stem cells, with implications that these changes will lead to sustained improvement of the tissue or system. Here, we examined the effect of elevating NAD⁺ levels in models with reduced hematopoietic stem cell (HSC) potential, ATM-deficient and aged WT mice, and showed that supplementation of nicotinamide riboside (NR), a NAD⁺ precursor, improved lymphoid lineage potential during supplementation. In aged mice, this improved lymphoid potential was maintained in competitive transplants and was associated with transcriptional repression of myeloid gene signatures in stem and lineage-committed progenitor cells after NR treatment. However, the altered transcriptional priming of the stem cells toward lymphoid lineages was not sustained in the aged mice after NR removal. These data characterize significant alterations to the lineage potential of functionally compromised HSCs after short-term exposure to NR treatment.

NAD ⁺补充剂在受损环境中具有显着益处，主要通过改善线粒体功能和 DNA 修复发挥作用。将 NAD ⁺提升到生理水平已被证明可以改善一些成体干细胞的功能，暗示这些变化将导致组织或系统的持续改善。在这里，我们检查了在造血干细胞 (HSC) 潜能降低、ATM 缺陷和衰老 WT 小鼠模型中提高 NAD ⁺水平的影响，并表明补充烟酰胺核苷 (NR)，一种 NAD ⁺前体，在补充期间改善淋巴谱系潜力。在老年小鼠中，这种改善的淋巴潜能在竞争性移植中得以维持，并且与 NR 治疗后干细胞和谱系定向祖细胞中髓样基因特征的转录抑制有关。然而，干细胞向淋巴谱系的转录启动的改变在去除 NR 后在老年小鼠中并未持续。这些数据表明，短期暴露于 NR 治疗后，功能受损的 HSC 的谱系潜力发生了显着变化。