CLASP2 safeguards hematopoietic stem cell properties during mouse and fish development

Cell Reports

Joris Maas¹  Catherine Robin¹  Thomas Clapes¹  Sreya Basu¹  Ihor Smal²  Laurent Yvernogeau³  Anna Klaus³  Bart Weijts³  Niels Galjart³ 

[1] University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands;Department of Cell Biology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands;;Hubrecht Institute-KNAW &

关键词: hematopoietic stem cells;    CLASP2;    hemogenic endothelium;    mouse;    zebrafish;    intra-aortic hematopoietic clusters;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown