Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection

The hematopoietic stem cell (HSC) niche provides essential microenvironmental cues for the production and maintenance of HSCs within the bone marrow. During inflammation, hematopoietic dynamics are perturbed, but it is not known whether changes to the HSC–niche interaction occur as a result. We visualize HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow following Trichinella spiralis infection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behavior: (a) a pattern of revisiting previously explored space and (b) a pattern of exploring new space. Whereas HSCs from control donors predominantly follow pattern (a), those from infected mice adopt both strategies. Using detailed computational analyses of cell migration tracks and life‐history theory, we show that the increased motility of HSCs following infection can, perhaps counterintuitively, enable mice to cope better in deteriorating HSC–niche microenvironments following infection. Stem Cells 2017;35:2292–2304 Hematopoietic stem cells (HSCs) are collected from infected and control mice and injected into recipient mice, where they are then imaged. HSCs are followed over time and their movement recorded. These tracks are then analyzed statistically, and the analysis shows that HSCs that have been exposed to Trichinella infection exhibit different migration behavior than those in control mice. These differences suggest that they are searching for suitable niches in their new context.