Hematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflammatory response of HSPCs to treatment (a total of 10,046 cells from four time points spanning the first 72 h of response) with the pro-inflammatory cytokine IFNα to investigate the HSPCs' dynamic changes during acute inflammation. We developed the essential novel computational approaches to process and analyze the resulting single-cell time series dataset. This includes an unbiased cell type annotation and abundance analysis post inflammation, tools for identification of global and cell type-specific responding genes, and a semi-supervised linear regression approach for response pseudotime reconstruction. We discovered a variety of different gene responses of the HSPCs to the treatment. Interestingly, we were able to associate a global reduced myeloid differentiation program and a locally enhanced pyroptosis activity with reduced myeloid progenitor and differentiated cells after IFNα treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFNα on the HSPCs.

中文翻译：

---

单细胞时间序列分析揭示了 HSPC 对炎症反应的动态。

众所周知，造血干细胞和祖细胞 (HSPC) 对急性炎症有反应；然而，人们对 HSPC 中这些应激反应的动态和异质性知之甚少。在这里，我们在 HSPC 对促炎细胞因子 IFNα 治疗（反应前 72 小时的四个时间点总共 10,046 个细胞）的炎症反应的感知、反应和恢复阶段进行了单细胞测序调查 HSPC 的情况急性炎症期间的动态变化。我们开发了基本的新颖计算方法来处理和分析所得的单细胞时间序列数据集。这包括无偏的细胞类型注释和炎症后丰度分析、用于识别全局和细胞类型特异性响应基因的工具，以及用于响应伪时间重建的半监督线性回归方法。我们发现 HSPC 对治疗有多种不同的基因反应。有趣的是，我们能够将整体减少的骨髓分化程序和局部增强的细胞焦亡活性与 IFNα 治疗后减少的骨髓祖细胞和分化细胞联系起来。总而言之，单细胞时间序列分析使我们能够公正地研究 IFNα 对 HSPC 的异质性和动态影响。