Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment

• DOI: 10.1084/jem.20091318
• Publication Date: 2010-04-27T02:18:47Z
• Authors: Yohei Morita; Hideo Ema; Hiromitsu Nakauchi
• Keywords: 0303 health sciences; Hematopoietic Stem Cell Transplantation; Nuclear Proteins; Antigens, CD34; Nerve Tissue Proteins; Receptors, Cell Surface; Hematopoietic Stem Cells; Article; Cell Compartmentation; Colony-Forming Units Assay; Mice, Inbred C57BL; Kinetics; Mice; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Ataxins; Signaling Lymphocytic Activation Molecule Family Member 1; Antigens, CD; Animals; Regeneration; Cell Lineage; Ataxin-1; Biomarkers

Hematopoietic stem cells (HSCs) have been extensively characterized based on functional definitions determined by experimental transplantation into lethally irradiated mice. In mice, HSCs are heterogeneous with regard to self-renewal potential, in vitro colony-forming activity, and in vivo behavior. We attempted prospective isolation of HSC subsets with distinct properties among CD34−/low c-Kit+Sca-1+Lin− (CD34−KSL) cells. CD34−KSL cells were divided, based on CD150 expression, into three fractions: CD150high, CD150med, and CD150neg cells. Compared with the other two fractions, CD150high cells were significantly enriched in HSCs, with great self-renewal potential. In vitro colony assays revealed that decreased expression of CD150 was associated with reduced erythroblast/megakaryocyte differentiation potential. All three fractions were regenerated only from CD150high cells in recipient mice. Using single-cell transplantation studies, we found that a fraction of CD150high cells displayed latent and barely detectable myeloid engraftment in primary-recipient mice but progressive and multilineage reconstitution in secondary-recipient mice. These findings highlight the complexity and hierarchy of reconstitution capability, even among HSCs in the most primitive compartment.