title: The non-canonical Wnt receptor Ryk regulates hematopoietic stem cell repopulation in part by controlling proliferation and apoptosis.
abstract: The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development. We show that there are dynamic changes in Ryk expression during development and in different hematopoietic tissues. Functionally, Ryk regulates NK cell development in a temporal fashion. Moreover, Ryk-deficient mice show diminished, but not absent self-renewal of hematopoietic stem cells (HSC), via effects on mildly increased proliferation and apoptosis. Thus, Ryk deficiency in HSCs from fetal liver reduces their quiescence, leading to proliferation-induced apoptosis and decreased self-renewal.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden, The Netherlands.
authors.forename: Farbod
authors.initials: F
authors.lastname: Famili
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden, The Netherlands.
authors.forename: Laura Garcia
authors.initials: LG
authors.lastname: Perez
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden, The Netherlands.
authors.forename: Brigitta Ae
authors.initials: BA
authors.lastname: Naber
authors.affiliation: Department of Molecular Cell biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jasprina N
authors.initials: JN
authors.lastname: Noordermeer
authors.affiliation: Department of Molecular Cell biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lee G
authors.initials: LG
authors.lastname: Fradkin
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden, The Netherlands.
authors.forename: Frank Jt
authors.initials: FJ
authors.lastname: Staal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D020794:Receptor Protein-Tyrosine Kinases; C118148:Ryk protein, mouse