Agonists of trained immunity induce epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) to generate long-lasting immune protection. Although trained HSPCs generate myeloid cells with increased responsiveness to secondary challenges, whether their differentiation kinetics is affected by prior exposure to inducers of trained immunity remains elusive. Here, we used lineage tracing to examine the cell fates of endothelial protein C receptor-positive hematopoietic stem cells (EPCR⁺ HSCs) and fms-like tyrosine kinase 3-positive multipotent progenitor cells (Flt3⁺ MPPs) in β-glucan-induced trained immunity. We found that although β-glucan triggered the expected expansion of myeloid progenitors, the differentiation behaviors of EPCR⁺ HSCs and Flt3⁺ MPPs in multiple cycles of hematopoietic regeneration were hardly affected. Thus, our results rule out changed kinetics in cell differentiation by EPCR⁺ HSC and Flt3⁺ MPP as the cause of enhanced myelopoiesis upon secondary immune challenges.

受过训练的免疫激动剂可诱导造血干细胞和祖细胞 (HSPC) 发生表观遗传变化，从而产生持久的免疫保护。尽管训练有素的 HSPC 生成的骨髓细胞对二次挑战的反应性增强，但它们的分化动力学是否受到先前暴露于训练有素的免疫诱导剂的影响仍然难以捉摸。在这里，我们使用谱系追踪来检查内皮蛋白 C 受体阳性造血干细胞 (EPCR ⁺ HSCs) 和 fms 样酪氨酸激酶 3 阳性多能祖细胞 (Flt3 ⁺ MPPs) 在 β-葡聚糖诱导训练中的细胞命运免疫。我们发现，尽管 β-葡聚糖触发了预期的骨髓祖细胞扩增，但 EPCR ⁺ HSC 和 Flt3的分化行为⁺多个造血再生周期中的 MPPs 几乎没有受到影响。因此，我们的结果排除了 EPCR ⁺ HSC 和 Flt3 ⁺ MPP 改变的细胞分化动力学是继发性免疫挑战后骨髓细胞生成增强的原因。