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

Abstract

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.