Emergency granulopoiesis is the enhanced and accelerated production of granulocytes that occurs during acute infection. The contribution of hematopoietic stem cells (HSCs) to this process was reported; however, how HSCs participate in emergency granulopoiesis remains elusive. Here, using a mouse model of emergency granulopoiesis we observe transcriptional changes in HSCs as early as 4 h after lipopolysaccharide (LPS) administration. We observe that the HSC identity is changed towards a myeloid-biased HSC and show that CD201 is enriched in lymphoid-biased HSCs. While CD201 expression under steady-state conditions reveals a lymphoid bias, under emergency granulopoiesis loss of CD201 marks the lymphoid-to-myeloid transcriptional switch. Mechanistically, we determine that lymphoid-biased CD201⁺ HSCs act as a first response during emergency granulopoiesis due to direct sensing of LPS by TLR4 and downstream activation of NF-κΒ signaling. The myeloid-biased CD201⁻ HSC population responds indirectly during an acute infection by sensing G-CSF, increasing STAT3 phosphorylation, and upregulating LAP/LAP* C/EBPβ isoforms. In conclusion, HSC subpopulations support early phases of emergency granulopoiesis due to their transcriptional rewiring from a lymphoid-biased to myeloid-biased population and thus establishing alternative paths to supply elevated numbers of granulocytes.

中文翻译：

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造血干细胞在紧急粒细胞生成的早期阶段经历淋巴向骨髓的转变

紧急粒细胞生成是急性感染期间发生的粒细胞生成的增强和加速。报道了造血干细胞（HSC）对此过程的贡献；然而，造血干细胞如何参与紧急粒细胞生成仍不清楚。在这里，使用紧急粒细胞生成的小鼠模型，我们早在脂多糖 (LPS) 给药后 4 小时就观察到 HSC 的转录变化。我们观察到 HSC 的身份向髓系偏向的 HSC 转变，并表明 CD201 在淋巴偏向的 HSC 中富集。虽然稳态条件下的 CD201 表达揭示了淋巴偏向，但在紧急粒细胞生成过程中，CD201 的缺失标志着淋巴向骨髓的转录转换。从机制上讲，我们确定，由于 TLR4 直接感知 LPS 和下游 NF-κB 信号传导，偏向淋巴的 CD201 ^{+ HSC 在紧急粒细胞生成过程中充当第一反应。}骨髓偏向的 CD201 ^- HSC 群体在急性感染期间通过感知 G-CSF、增加 STAT3 磷酸化和上调 LAP/LAP* C/EBPβ 亚型来间接做出反应。总之，HSC 亚群支持紧急粒细胞生成的早期阶段，因为它们的转录重新布线从淋巴偏向到髓系偏向，从而建立了供应大量粒细胞的替代途径。