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Abstract
The traditional view of hematopoiesis has been that all the cells of the peripheral
blood are the progeny of a unitary homogeneous pool of hematopoietic stem cells (HSCs).
Recent evidence suggests that the hematopoietic system is actually maintained by a
consortium of HSC subtypes with distinct functional characteristics. We show here
that myeloid-biased HSCs (My-HSCs) and lymphoid-biased HSCs (Ly-HSCs) can be purified
according to their capacity for Hoechst dye efflux in combination with canonical HSC
markers. These phenotypes are stable under natural (aging) or artificial (serial transplantation)
stress and are exacerbated in the presence of competing HSCs. My- and Ly-HSCs respond
differently to TGF-beta1, presenting a possible mechanism for differential regulation
of HSC subtype activation. This study demonstrates definitive isolation of lineage-biased
HSC subtypes and contributes to the fundamental change in view that the hematopoietic
system is maintained by a continuum of HSC subtypes, rather than a functionally uniform
pool.
2010 Elsevier Inc. All rights reserved.