CORRESPONDENCE

Hematopoietic stem cells (HSCs) function to maintain blood homeostasis throughout life via their unique ability to differentiate into all blood cell types and to self-renew. These prop-erties, along with the robust ability of HSCs to engraft myeloablated recipients in the setting of BM transplantation, have established the clinical paradigm for therapeutic stem cell use (Weissman, 2000). Originally described by Till and McCulloch (1961), HSCs were first experimentally defined by their ability to form macroscopic colonies in the spleens (CFU-S) of irradiated recipients after BM transplantation that histological examina-tion revealed contained multiple blood lineages, and cytological examination revealed were clonally derived (Becker et al., 1963). Together with the demonstration that a subset of CFU-S colonies had the potential to reform colonies when transplanted into secondary recipients (Siminovitch et al., 1963), the defining proper-ties of hematopoietic stem cells—multipotency and self-renewal—were established. In the 50 yr since these seminal studies were conducted, the experimental study of HSCs has flourished, leading to a profound level of understanding of their biology. These efforts were enabled through the development of several in vivo and in vitro assays that permitted evaluation of HSC self-renewal and multilineage potential, and by meth-ods that allowed purification of HSCs by FACS. HSCs were initially reported to be enriched within the Thy1lowLineage fraction of the murine BM (Muller-Sieburg et al., 1986), and subsequently cells with a Thy1lowLineageSca1