Progenitor Effect in the spleen drives early recovery via Universal Hematopoietic Inflation [scMultiome]

Hematopoietic stem cells (HSC) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remains an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery. Here, we uncovered the spatiotemporal dynamics of early active hematopoiesis, “Hematopoietic Inflation”, using a highly sensitive in vivo imaging system and established universal HSPCs capable of immediately supplying vast numbers of blood cells. Hematopoietic Inflation occurs in three peaks in the spleen after transplantation, with common myeloid progenitors (CMPs), notably characterized by HSC-like signatures, playing a central role. Leveraging these findings, we developed expanded CMPs (exCMPs), characterized by a gene expression pattern that selectively proliferates in the spleen and promotes hematopoietic expansion. Moreover, universal exCMPs supported early hematopoiesis in allogeneic transplantation. Human universal exCMPs have the potential to be a viable therapeutic enhancement for all HSC transplant patients.