Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration
Résumé
Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. At
the top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features are
controlled through key microenvironmental cues and regulatory pathways, such as Wnt signaling.We showed previously that PTK7,
a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesis
has remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, with
the highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss of
Ptk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlated
with increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling novel
and unexpected functions for planar cell polarity pathways in HSC fate.
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