Possible scenarios for the underlying mechanism governing the spatial and functional interactions between HSCs and their BM niches. Graphical overview of different mechanisms of HSC-niche interactions requiring active HSC migration or niche induction. One proposed mechanism suggests that HSCs actively migrate toward spatially distinct, predefined BM locations and establish stable cell-cell interactions with specific niche populations (blue), whereas other BM niches are distally located and may regulate HSC behavior via secreted factors (gray). Alternatively, HSCs actively migrate and establish transient interactions with defined BM niches in spatially distinct locations or only require exposure to immobilized molecular signals (depending on HSC motility). Considering the transcriptional heterogeneity of BM populations, HSCs may interact with spatially and functionally distinct BM subpopulations, which are currently unknown. In addition, HSCs may induce their own niche by transcriptionally reprogram their neighboring BM populations into functional HSC niches. A combination of these mechanisms or the presence of additional scenarios is also possible (marked by the question mark).