Numerous niches for hematopoietic stem cells remain empty during homeostasis

Hematopoietic stem cells (HSCs) reside in and are maintained by special microenvironments, termed niches. It is assumed that the HSC niche space remains occupied by endogenous cells and that myelosuppressive conditioning is required to achieve high levels of HSC engraftment. We herein demonstrate that upon the transplantation of very large numbers of purified HSCs into normal mice not exposed to myeloablation, donor HSCs engrafted in niches distant from filled HSC niches without replacing host HSCs and subsequently proliferated and generated hematopoietic progenitors, leading to marked increases in the overall HSC numbers in bone marrow. Additionally, stem cell factor that is produced by CXC chemokine ligand 12-abundant reticular cells is involved in HSC engraftment. In contrast, host granulocyte/macrophage progenitors (GMPs) were replaced by the progeny of transplanted donor HSCs, and overall GMP numbers remained unchanged. Thus, inconsistent with the classical concept, numerous empty HSC niches are available for engraftment and proliferation in bone marrow.