CLASP2 safeguards hematopoietic stem cell properties during mouse and fish development

Hematopoietic stem cells (HSCs) express a large variety of cell surface receptors that are associated with acquisition of self-renewal and multipotent properties. Correct expression of these receptors depends on a delicate balance between cell surface trafficking, recycling, and degradation and is controlled by the microtubule network and Golgi apparatus, whose roles have hardly been explored during embryonic/fetal hematopoiesis. Here we show that, in the absence of CLASP2, a microtubule-associated protein, the overall production of HSCs is reduced, and the produced HSCs fail to self-renew and maintain their stemness throughout mouse and zebrafish development. This phenotype can be attributed to decreased cell surface expression of the hematopoietic receptor c-Kit, which originates from increased lysosomal degradation in combination with a reduction in trafficking to the plasma membrane. A dysfunctional Golgi apparatus in CLASP2-deficient HSCs seems to be the underlying cause of the c-Kit expression and signaling imbalance. [Display omitted] •CLASP2 regulates HSC production throughout mouse and zebrafish development•CLASP2 prevents premature HSC differentiation and loss of self-renewal properties•CLASP2 controls Golgi apparatus integrity and c-Kit degradation and trafficking in HSCs Klaus et al. establish a conserved function for the microtubule-associated protein CLASP2 in HSC generation, maturation, and expansion throughout mouse and zebrafish development. They propose that CLASP2 acts by maintaining Golgi integrity and controlling the correct level of the essential HSC receptor c-Kit on the plasma membrane.