Revised model of Lin^–Sca1⁺kithi HSC hierarchy based on differential expression of CD34, flt3, and c-mpl. LT-HSCs (blue) differentiate into ST-HSCs (red) with reduced self-renewing capacity but enhanced ability to rapidly reconstitute myelopoiesis. The ST-HSC gives rise to a multipotent progenitor (MPP; green) with sustained lymphomyeloid potential, but that on transplantation rapidly and preferentially reconstitutes lymphopoiesis rather than myelopoiesis. Direct comparisons are made with 2 previous key studies on LT-HSCs and ST-HSCs.^7,17  Nakauchi and coworkers⁷  defined ST-HSCs as LSKCD34⁺ cells, without further subfractionation. Weissman and coworkers¹⁷  defined LT-HSCs as LSKflt3^–, which the present studies show can be subfractionated into LSKCD34^–flt3^– LT-HSCs and LSKCD34⁺flt3^– ST-HSCs. In addition, the population of LSKflt3⁺Thy1.1^lo ST-HSCs¹⁷  is likely to overlap with the population of LSKCD34⁺flt3⁺ MPPs. Expression of c-mpl (TPO receptor) of different subpopulations is based on the present studies of TPO responsiveness and previous studies of c-mpl expression on HSCs.²⁵