In March 2023, a study led by the team of Professor Tao Cheng from the Blood Disease Hospital of the Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) was published in the prestigious international academic journal Science Immunology (IF=30.63). The research, titled "Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation," utilized single-cell analysis techniques to investigate the dynamic process of hematopoietic reconstitution in patients undergoing allogeneic hematopoietic stem cell transplantation. The findings not only provide insights into the regenerative process of transplanted hematopoietic stem/progenitor cells (HSPCs) but also offer guidance for future research and clinical interventions in the field of hematopoietic stem cell transplantation (HSCT). This study was recently recognized as one of the "Top Ten Advances in Hematology in China in 2023."
Hematopoietic stem cell transplantation (HSCT) is a regenerative therapy used to treat various malignant, inherited, or autoimmune diseases. Despite its success, the understanding of hematopoietic reconstitution in transplant patients remains limited. In this study, the researchers aimed to uncover the dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at the single-cell level after transplantation.
The researchers performed single-cell RNA sequencing (scRNA-seq) on HSPCs and total nucleated cells (TNCs) collected from patients with aplastic anemia receiving allogeneic peripheral blood stem cell transplantation. They also analyzed whole-exome sequencing data to identify donor chimerism based on single-nucleotide polymorphisms (SNPs).
The study revealed several key findings. Firstly, the HSPCs underwent rapid changes during the first 30 days after transplantation, with a strong proliferative response observed on the first day. Transcriptomic analysis allowed the researchers to identify immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family, which were enriched in the granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) showed lower levels of these immunoregulatory neutrophil progenitors.
Furthermore, the dynamics of hematopoietic stem and progenitor cells were analyzed using trajectory inference, revealing the lineage bias and proliferation tendencies of different cell subsets. The researchers also identified residual cells in the recipient samples based on single-cell chimerism analysis, highlighting the reliability of their transcriptomics-based method.
This study provides valuable insights into the regenerative process of transplanted HSPCs in human patients. The findings shed light on the dynamics of hematopoietic reconstitution, including the lineage priming and proliferation patterns of HSPCs at different time points after transplantation. The identification of immunoregulatory neutrophil progenitors and their correlation with aGVHD risk may help in early identification of patients at high risk for developing aGVHD.
In summary, this study utilized single-cell analysis techniques to investigate the dynamics of hematopoietic reconstitution in patients undergoing allogeneic hematopoietic stem cell transplantation. The findings provide important insights into the regenerative process of transplanted HSPCs and may guide future research and clinical interventions in the field of HSCT.
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