The many faces of hematopoietic stem cell heterogeneity

All hematopoietic stem cells (HSCs) are not alike. They differ in their physical characteristics such as cell cycle status and cell surface marker phenotype, they respond to different extrinsic signals, and they have different lineage outputs following transplantation. The growing evidence that supports heterogeneity within HSCs, the most robust cell fraction at the foundation of the adult hematopoietic system, is of high current interest and raises questions as to why HSC subtypes exist, how they are generated and whether HSC heterogeneity affects leukemogenesis or treatment options. This Review provides a developmental overview of HSC subtypes during embryonic, fetal and adult stages of hematopoiesis and discusses the possible origins and consequences of HSC heterogeneity.