title: Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration.
abstract: 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.
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Polarité Cellulaire, Signalisation Cellulaire et Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM, U1068, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Lhoumeau
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and Centre de Recherche en Cancérologie de Marseille, Molécules d'Adhérence Jonctionnelles dans Host/Tumeur Interactions, INSERM, U1068, Marseille F-13009, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Arcangeli
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and Centre de Recherche en Cancérologie de Marseille, Molécules d'Adhérence Jonctionnelles dans Host/Tumeur Interactions, INSERM, U1068, Marseille F-13009, France.
authors.forename: Maria
authors.identifier: 0000-0001-6465-8723
authors.initials: M
authors.lastname: De Grandis
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Polarité Cellulaire, Signalisation Cellulaire et Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM, U1068, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Giordano
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Polarité Cellulaire, Signalisation Cellulaire et Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM, U1068, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Orsoni
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Polarité Cellulaire, Signalisation Cellulaire et Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM, U1068, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lembo
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and Centre de Recherche en Cancérologie de Marseille, Molécules d'Adhérence Jonctionnelles dans Host/Tumeur Interactions, INSERM, U1068, Marseille F-13009, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Bardin
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Polarité Cellulaire, Signalisation Cellulaire et Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM, U1068, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Marchetto
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and Centre de Recherche en Cancérologie de Marseille, Molécules d'Adhérence Jonctionnelles dans Host/Tumeur Interactions, INSERM, U1068, Marseille F-13009, France.
authors.forename: Michel
authors.identifier: 0000-0002-8361-3034
authors.initials: M
authors.lastname: Aurrand-Lions
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Polarité Cellulaire, Signalisation Cellulaire et Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM, U1068, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009, France; Université d'Aix-Marseille, Marseille F-13284, France; and jean-paul.borg@inserm.fr.
authors.forename: Jean-Paul
authors.identifier: 0000-0001-8418-3382
authors.initials: JP
authors.lastname: Borg
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D049109:Cell Proliferation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C486452:Ptk7 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases