Mende et al use a variety of Cre lines targeting multiple nonhematopoietic cells of the BM microenvironment. They attempt to resolve previous discrepancies in the field whereby the overlap between niche cells targeted by different Cre lines was underestimated because only subsets among those Cre-targeted cells had been characterized. To achieve their goal, they used several reporters and performed RNA sequencing from immunophenotypically identified HSPCs, mesenchymal stromal cells, endothelial cells, and preosteoblasts isolated from bone-associated (endosteal) BM or located further from bone (central). Matching top expressed ligands in niche cells with the most highly expressed receptors on HSPCs provides a candidate HSPC-niche interactome containing some old and many new potential HSPC regulators.