Affiliation:
1. National Clinical Research Center for Hematologic Disease Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Peking University People's Hospital Peking University Institute of Hematology Peking University Beijing 100044 China
2. Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences Beijing 2019RU029 China
3. Peking‐Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China
Abstract
AbstractAllogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a widely used treatment for a variety of hematopoietic disorders, and also provides a valuable platform for investigating the development of donor‐derived immune cells in recipients post‐HSCT. The immune system remodels from the donor to the recipient during allo‐HSCT. However, little is known about the cell profile alterations as donor homeostasis rebalances to recipient homeostasis following HSCT. Here, multi‐omics technology is applied at both the single cell and bulk sample levels, as well as spectrum flow cytometry and fluorescent transgenic mouse models, to dissect the dynamics of the rebalanced homeostatic immune system in recipients after allo‐HSCT. The data reveal that all immune subpopulations observed in donors are successfully restored in recipients, though with varying levels of abundance. The remodeling of immune homeostasis exhibits different patterns in HLA‐matched and haploidentical HSCT, highlighting distinct biases in T cell reconstitution from the central and peripheral pathways. Furthermore, ZNF683 is critical for maintaining the persistence and quiescence of CD8 T‐cell in haploidentical HSCT. The research can serve as a foundation for developing novel strategies to induce immune tolerance.
Funder
National Natural Science Foundation of China