研究动态
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人类异基因造血干细胞移植后血液再生的单细胞分离。

Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation.

发表日期:2023 Mar 17
作者: Yingying Huo, Linjie Wu, Aiming Pang, Qing Li, Fang Hong, Caiying Zhu, Zining Yang, Weiqian Dai, Yawei Zheng, Qianqian Meng, Jiali Sun, Shihui Ma, Linping Hu, Ping Zhu, Fang Dong, Xin Gao, Erlie Jiang, Sha Hao, Tao Cheng
来源: Experimental Hematology & Oncology

摘要:

造血干细胞移植是治疗许多恶性、遗传或自身免疫疾病的有效再生疗法。然而,我们对移植患者再生造血的理解仍然有限。在这里,我们发现人类同种异体造血干细胞和祖细胞(HSPC)在移植后的单个细胞分辨率下的再生构成动力学。移植的HSPC在移植后的前30天经历了快速而可测的变化,特点是在第一天表现出强烈的增殖反应。HSPC的转录组分析使我们能够观察到,表达高水平的S100A基因家族的免疫调节性嗜中性粒细胞祖细胞在粒细胞集落刺激因子移动的外周血干细胞中富集。移植受者发展急性移植物抗宿主病(aGVHD)的人,注入的S100A高表达的免疫调节性嗜中性粒细胞祖细胞,免疫表型为Lin-CD34+CD66b+CD177+,比那些没有发展aGVHD的人少。因此,我们的研究提供了关于人类患者移植后HSPC再生过程的洞见,并确定了一个可能的标准,用于在移植后早期识别高风险发展aGVHD的患者。
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 S100Ahigh 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.