Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration

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Lhoumeau, Anne-Catherine | Arcangeli, Marie-Laure | de Grandis, Maria | Giordano, Marilyn | Orsoni, Jean-Christophe | Lembo, Frédérique | Bardin, Florence | Marchetto, Sylvie | Aurrand-Lions, Michel | Borg, Jean-Paul

Edité par CCSD ; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists -

International audience. Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. Atthe top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features arecontrolled 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 hematopoiesishas remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, withthe highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss ofPtk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlatedwith increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling noveland unexpected functions for planar cell polarity pathways in HSC fate.

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