α1,3-fucosylation treatment improves cord blood CD34 negative hematopoietic stem cell navigation

For almost two decades, clinicians have overlooked the diagnostic potential of CD34^neg hematopoietic stem cells because of their limited homing capacity relative to CD34^posHSCs when injected intravenously. This has contributed to the lack of appeal of using umbilical cord blood in HSC transplantation because its stem cell count is lower than bone marrow. The present study reveals that the homing and engraftment of CD34^negHSCs can be improved by adding the Sialyl Lewis X molecule via α1,3-fucosylation. This unlocks the potential for using this more primitive stem cell to treat blood disorders because our findings show CD34^negHSCs have the capacity to regenerate cells in the bone marrow of mice for several months. Furthermore, our RNA sequencing analysis revealed that CD34^negHSCs have unique adhesion pathways, downregulated in CD34^posHSCs, that facilitate interaction with the bone marrow niche. Our findings suggest that CD34^neg cells will best thrive when the HSC resides in its microenvironment.