Abstract: The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSC/HSPC) biology. Interactions between the niche and stem cells have been difficult to track, but recent advances marking fluorescent HSCs/HSPCs with specific fluorescent reporter transgenes and the use of advanced imaging techniques have allowed exquisite visualization in the caudal hematopoietic tissue (CHT) of the developing zebrafish.
Sinusoidal endothelial cells interact closely with HSCs as they engraft in this niche. We performed a gain-of-function screen and identified the angiogenic chemokine, CXCL8, and its receptor, CXCR1, as positive regulators of HSC engraftment. Single-cell tracking experiments demonstrated that this pro-engraftment effect of CXCL8/CXCR1 signaling is due to a 25% increase in CHT residency time, allowing 1.8 fold more HSC cell divisions to occur within the CHT.
Using three-dimensional reconstruction of the CHT, we showed that enhanced CXCL8/CXCR1 signaling was associated with a 21% increase in the volume of the CHT, likely favoring HSC engraftment. These findings highlight the power of advanced imaging in combination with zebrafish genetics to uncover novel mechanisms of stem cell-microenvironment interactions.