Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor–mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100A high immunoregulatory neutrophil progenitors, immunophenotyped as Lin - CD34 + CD66b + CD177 + , than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.

中文翻译：

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异基因造血干细胞移植后人类造血重建的单细胞解剖

造血干细胞移植是治疗许多恶性、遗传性或自身免疫性疾病的有效再生疗法。然而，我们对移植患者重建造血的了解仍然有限。在这里，我们揭示了移植后人类同种异体造血干细胞和祖细胞 (HSPC) 在单细胞分辨率下的重建动力学。移植的 HSPC 在移植后的前 30 天内经历了快速且可测量的变化，其特点是第一天的强烈增殖反应。HSPC 的转录组学分析使我们能够观察到免疫调节中性粒细胞祖细胞表达高水平的S100A基因家族在粒细胞集落刺激因子动员的外周血干细胞中富集。发生急性移植物抗宿主病 (aGVHD) 的移植受者输注的 S100A 较少高的免疫调节中性粒细胞祖细胞，免疫表型为 Lin-CD34+CD66b+CD177+, 比那些没有发展 aGVHD 的人。因此，我们的研究提供了对人类患者移植 HSPCs 再生过程的见解，并确定了一个潜在的标准，用于识别移植后早期发生 aGVHD 的高风险患者。