In situ mapping identifies distinct vascular niches for myelopoiesis

In contrast to virtually all other tissues, the anatomy of differentiation in the bone marrow (BM) remains unknown. This is due to a lack of strategies to examine blood cell production in situ, which are required to understand differentiation, lineage commitment decisions, and define how spatial organizing cues inform tissue function. Here we developed approaches to image myelopoiesis and generated atlases of granulocyte and monocyte/dendritic cell differentiation. Granulopoiesis and dendritic/monopoiesis localize to different sinusoids and display lineage-specific spatial and clonal architectures. Acute systemic L. monocytogenes infection induces lineage-specific progenitor clusters through increased progenitor self-renewal, but the different lineages remain spatially separated. Monocyte dendritic cell progenitors (MDP) map with Ly6C(lo) monocytes and conventional dendritic cells; these localize to a subset of vessels expressing a major regulator of myelopoiesis(1) colony-stimulating-factor 1 (CSF1/ M-CSF). Specific deletion of Csf1 in endothelium disrupted the architecture around MDP and their localization to sinusoids. Subsequently, there were reduced MDP numbers and differentiation ability, and loss of Ly6C(lo) monocytes and dendritic cells during homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for specific spatial organization of definitive hematopoiesis.