The fleet feet of haematopoietic stem cells: rapid motility, interaction and proteopodia

Haematopoietic stem cells (HSCs) have been extensively characterized regard ing in vivo engraftment, surface epitopes and genetic regulation. However, little is known about the homing of these rare cells, and their intrinsic m otility and membrane deformation capacity. We used high-speed optical-secti oning microscopy and inverted fluorescent videomicroscopy to study highly p urified murine lineage-negative. rhodamine-low Hoechst-tow HSCs over time u nder various in vitro conditions. We discovered extremely rapid motility, d irected migration to stromal cells and marked membrane modulation. High res olution images with three-dimensional reconstruction showed the general pre sence of microspikes. Further, pseudopodia (proteopodia) were observed that were induced by stromal-derived factor-1 and steel factor. Proteopodia wer e directed towards and were quenched by stromal cells, at times bridged HSC s, and could rapidly retract or detach from cells, Proteopodia were also ob served in vivo with homed HSCs in frozen sections of murine spleen, lung an d heart. This is the first demonstration that HSCs are both fast and highly malleable in phenotype.