[Clonal trajectories of post-transplant hematopoiesis]

Hematopoiesis relies on self-renewing hematopoietic stem and more committed progenitor cells (HSPCs), which occurs in specialized niches. Their transplantation can effectively treat malignant blood disorders and genetic diseases, thanks to advances in HLA typing, cell sources, and conditioning regimens. Clonal tracing reveals a biphasic pattern of hematopoietic reconstitution following transplantation, with initial contribution from short-term progenitors followed by long-term multi-potent hematopoietic stem cells (HSCs). Reconstituted hematopoiesis remains polyclonal, and is influenced by donor age, pathological context, and genetic history. Transplantation does not increase the mutational burden but induces clonal selection, leading to reduced clonal diversity, especially with HSPC from older donors. These results validate HSPC-based gene therapy and open new prospects for optimizing donor selection, conditioning regimens, and personalized patient care.