Distinct cell cycle activity in fetal, adult, and old HSCs. HSC cell cycle activity and cellular output is highly dynamic throughout the lifetime of an organism. During fetal life (left column), HSCs display a high level of cell cycle activity, as their primary role at this stage is the genesis of the nascent blood system. During adult life (center column), HSCs reside in the BM and enter a predominantly quiescent (G₀) state, generating a balanced myeloid, erythroid, and lymphoid output to maintain blood homeostasis. As individuals age (right column), HSCs appear to remain predominantly quiescent, but their function begins to degrade (dotted outlines), resulting in the loss of erythroid and lymphoid output and bias toward the myeloid lineage. AGM: aorta-gonad-mesonephros; ND: not determined. See text for detailed discussion and references.