研究动态
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利用单细胞RNA测序方法对比分析臍带血和骨髓的差别及移植后的临床表现

Aligning the Cord Blood-Bone Marrow Differences and the Post-transplantation Clinical Manifestations by Single-Cell RNA-Seq.

发表日期:2023
作者: Jiali Wang, Yaping Wang, Yong Xu, Wenfeng Fu, Liucheng Rong, Yao Xue, Yongjun Fang
来源: Bone & Joint Journal

摘要:

脐带血移植是一种有前景的治疗血液恶性肿瘤的方法,因其强大的移植物抗白血病效应和低发生移植物抗宿主病的概率而备受关注。然而,延迟植入引起的感染风险限制了其临床应用。本研究通过比较单细胞RNA测序技术分析脐带血、骨髓和粒细胞集落刺激因子前处理骨髓的数据,以全面了解这些移植物之间的差异,并验证一些与我们接受移植的患者的临床数据相一致的差异。我们关注涉及造血重建和免疫重建的关键细胞类型的生物学特征。通过比较造血干/祖细胞(HSPCs)的寻道信号和分化潜能,我们发现相比于骨髓,脐带血中HSPCs含量较低,寻道能力较弱但具有更高的干细胞特性。此外,脐带血中的幼稚T细胞比例较高,而骨髓中的效应器和记忆T细胞丰度较高。值得注意的是,脐带血中的CD4+幼稚T细胞易于分化为调节性T细胞。在新抗原的刺激下,脐带血中T细胞与抗原呈递细胞之间的免疫激活作用较强,包括CD40_CD40LG、IL16_CD4等。在我们的临床数据中,移植后T细胞的亚群变化和单核细胞的状态与上述单细胞RNA测序研究的结果一致。脐带血作为一种新生命系统,发育不完全且活跃;多个机制有助于其良好的抗肿瘤效应,并可以应用于其他移植物。这些发现为发展血液恶性肿瘤治疗的新策略提供了启示。
Cord blood (CB) transplantation is a promising treatment for hematologic malignancies due to its strong graft-versus-leukemia effect and a low incidence of graft-versus-host disease. However, the risk of infection caused by delayed engraftment has limited its clinical application. In this study, we compared the single-cell RNA-seq of CB, bone marrow (BM), and granulocyte colony-stimulating factor primed BM to understand the differences between these grafts from a comprehensive view, and verified some differences in our clinical data of patients receiving transplantation. We focused on the biological features of key cell types involving the hematopoietic reconstitution and immune reconstitution. Based on the comparison of homing signal and differentiation potential of hematopoietic stem/progenitor cells (HSPCs), CB exhibited a lower content of HSPCs with weaker homing ability but higher stemness than BM. In addition, CB had a higher proportion of naïve T cells, while BM had a higher abundance of effector and memory T cells. Notably, the CD4+ naïve T cells in CB were prone to differentiate into Tregs. In response to neoantigens, the immune activation interactions between T cells and antigen-presenting cells were strong in CB, including CD40_CD40LG, IL16_CD4, and so on. In our clinical data, the subpopulation variations of T cells and the status of monocytes after transplantation were consistent with the results of the single-cell RNA-seq study above. CB, as a new birth system, is immature and active; several mechanisms contribute to its good anti-tumor effect, which can be introduced to other grafts. These findings provide insights into the development of new strategies for hematologic malignancies treatment.