Anniversary Review Series: Perspectives on the modern exploration of Experimental Hematology Heterogeneity and hierarchy of hematopoietic stem cells

Hematopoietic stem cells (HSCs) are a more heterogeneous population than previously thought. Extensive analysis of reconstitution kinetics after transplantation allows a new classifications of HSCs based on lineage balance. Previously unrecognized classes of HSCs, such as myeloid- and lymphoid-biased HSCs, have emerged. However, varying nomenclature has been used to describe these cells, promoting confusion in the field. To establish a common nomenclature, we propose a reclassification of short-, intermediate-, and long-term (ST, IT, and LT) HSCs defined as: ST ! 6 months, IT O 6 months, and LT O 12. We observe that myeloidbiased HSCs or a cells overlap with LT-HSCs, whereas lymphoid-biased HSCs or g/d cells overlap with ST-HSCs, suggesting that HSC lifespan is linked to cell differentiation. We also suggest that HSC heterogeneity prompts reconsideration of long-term (O4 months) multilineage reconstitution as the gold standard for HSC detection. In this review, we discuss relationships among ST-, IT-, and LT-HSCs relevant to stem cell heterogeneity, hierarchical organization, and differentiation pathways. 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.