A Gata1 enhancer–based model for the rescue of the hematopoietic defects induced by the Gata1^low mutation. Normal quiescent cKit^pos hematopoietic stem cells (HSC_G0) adhere to the endosteum of the bone^2-4  and do not express GFP (Figure 4). Once these cells are induced into cycle, they leave the osteoblast niche to lodge in the vascular niche of the marrow and begin the commitment process leading to the generation of common myeloid progenitors (CMPs), granulomonocytic progenitors (GMPs), and megakaryocytic-erythroid progenitors (MEPs).²⁹  Expression of Gata1 in these progenitors is driven by the HS1 enhancer.⁴⁷  By contrast, in Gata1^low mice, a higher proportion of the cKit^pos cells adheres to the osteoblast niche. These cells are GFP^pos and, therefore, have the potential to activate the HS2 enhancer. Because Gata1^lowcKit^pos cells do not express CXCR4,²⁴  once induced to cycle, they can no longer lodge in the vascular niche in the marrow. These cells, however, retain the ability to lodge in the spleen microenvironment (Figures 3 and 5), which is capable of sustaining maturation of those Gata1^low stem/progenitor cells that express Gata1 through the HS2 enhancer (Figure 4). This spleen-specific maturation route occurs through an alternative pathway that involves the generation of bipotent precursor for the erythroid/megakaryocytic lineage (PEM)^31-33  (and this paper). It is possible that the adhesion receptor, expressed by the HS2-Gata1 stem cell (X), and its ligand, expressed by the cells in the spleen microenvironment (XL) that mediate this interaction, are represented by BMP4 and Hedgehog, respectively.⁴⁰