Deciphering bone marrow engraftment after allogeneic stem cell transplantation in humans using single-cell analyses

Area of Science:

• Hematology
• Immunology
• Oncology

Background:

• Donor cell engraftment is crucial for allogeneic hematopoietic stem cell transplantation (HSCT).
• Peripheral blood analysis shows early myeloid recovery and T/B cell lymphopenia post-HSCT.
• Cellular networks in bone marrow during allogeneic engraftment remain poorly understood.

Purpose of the Study:

• To characterize the bone marrow cellular networks associated with allogeneic donor cell engraftment.
• To investigate the cellular and molecular changes in the bone marrow microenvironment post-HSCT.

Main Methods:

• Mass cytometry and CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) were used.
• Bone marrow cells were analyzed 3 months after HSCT in acute myelogenous leukemia patients.
• Comparison was made between 26 transplant recipients and 20 healthy controls.

Main Results:

• Profound alterations in myeloid and B cell progenitors were observed, with a shift towards terminal myeloid differentiation.
• Unsupervised analysis identified two recipient groups, one associated with graft-versus-host disease.
• Hematopoiesis was supported by myeloid/erythroid progenitors amidst monocyte, NK, and T cell-driven inflammation.
• Gene expression highlighted TNF-α signaling and IFN-γ response pathways.
• Allograft rejection signatures were prevalent, particularly in patients with prior graft-versus-host disease.

Conclusions:

• Allogeneic donor cell engraftment in bone marrow is characterized by emergency hematopoiesis.
• This process occurs within an inflammatory context driven by the allogeneic response.
• Understanding these cellular networks is key to improving HSCT outcomes.