Hematopoietic stem cells (HSCs) enable hematopoietic stem cell transplantation (HCT) through their ability to replenish the entire blood system. Proliferation of HSCs is linked to decreased reconstitution potential, and a precise regulation of actively dividing HSCs is thus essential to ensure long-term functionality. This regulation becomes important in the transplantation setting where HSCs undergo proliferation followed by a gradual transition to quiescence and homeostasis. Although mouse HSCs have been well studied under homeostatic conditions, the mechanisms regulating HSC activation under stress remain unclear. Here, we analyzed the different phases of regeneration after transplantation. We isolated bone marrow from mice at 8 time points after transplantation and examined the reconstitution dynamics and transcriptional profiles of stem and progenitor populations. We found that regenerating HSCs initially produced rapidly expanding progenitors and displayed distinct changes in fatty acid metabolism and glycolysis. Moreover, we observed molecular changes in cell cycle, MYC and mTOR signaling in both HSCs, and progenitor subsets. We used a decay rate model to fit the temporal transcription profiles of regenerating HSCs and identified genes with progressively decreased or increased expression after transplantation. These genes overlapped to a large extent with published gene sets associated with key aspects of HSC function, demonstrating the potential of this data set as a resource for identification of novel HSC regulators. Taken together, our study provides a detailed functional and molecular characterization of HSCs at different phases of regeneration and identifies a gene set associated with the transition from proliferation to quiescence.

造血干细胞 (HSC) 通过补充整个血液系统的能力实现造血干细胞移植 (HCT)。HSC 的增殖与重构潜力降低有关，因此，精确调控活跃分裂的 HSC 对于确保长期功能至关重要。这种调节在移植环境中变得很重要，在移植环境中，造血干细胞经历增殖，然后逐渐过渡到静止和稳态。尽管小鼠 HSC 在稳态条件下已得到充分研究，但应激条件下调节 HSC 激活的机制仍不清楚。在这里，我们分析了移植后再生的不同阶段。我们在移植后 8 个时间点从小鼠中分离骨髓，并检查干细胞和祖细胞群的重建动态和转录谱。我们发现再生的 HSC 最初产生快速扩增的祖细胞，并在脂肪酸代谢和糖酵解方面表现出明显的变化。此外，我们观察到 HSC 和祖细胞亚群中细胞周期、MYC 和 mTOR 信号传导的分子变化。我们使用衰减率模型来拟合再生 HSC 的时间转录谱，并识别移植后表达逐渐减少或增加的基因。这些基因在很大程度上与已发表的与 HSC 功能关键方面相关的基因集重叠，证明了该数据集作为识别新型 HSC 调节因子的资源的潜力。总而言之，我们的研究提供了 HSC 在不同再生阶段的详细功能和分子特征，并确定了与从增殖到静止过渡相关的基因组。