Because hematopoietic stem cells (HSCs) were found to require a bone marrow (BM) habitat for long-term function, many studies have attempted to dissect key cellular and molecular interactions between HSCs and their BM microenvironments or HSC niches. In this issue of Blood, Mende et al provide a computational method to infer potential ligand-receptor interactions between murine hematopoietic stem and progenitor cells (HSPCs) and their niche-forming cells.