'Cell-ebrating' diversity in the bone marrow niche: Classic and novel strategies to uncover niche composition

Our view on the role and composition of the bone marrow (BM) has dramatically changed over time from a simple nutrient for the bone to a highly complex multicellular tissue that sustains haematopoiesis. Among these cells, multipotent haematopoietic stem cells (HSCs), which are predominantly quiescent, possess unique self-renewal capacity and multilineage differentiation potential and replenish all blood lineages to maintain lifelong haematopoiesis. Adult HSCs reside in specialised BM niches, which support their functions. Much effort has been put into deciphering HSC niches due to their potential clinical relevance. Multiple cell types have been implicated as HSC-niche components including sinusoidal endothelium, perivascular stromal cells, macrophages, megakaryocytes, osteoblasts and sympathetic nerves. In this review we provide a historical perspective on how technical advances, from genetic mouse models to imaging and high-throughput sequencing techniques, are unveiling the plethora of molecular cues and cellular components that shape the niche and regulate HSC functions.