title: Hematopoietic stem cell fate decisions are regulated by Wnt antagonists: comparisons and current controversies.
abstract: Wingless and int (Wnt) proteins are secreted proteins that are important for regulating hematopoietic stem cell self-renewal and differentiation in the bone marrow microenvironment in mice. The mechanisms by which Wnt signaling regulates these hematopoietic cell fate decisions are not fully understood. Secreted Wnt antagonists, which are expressed in bone and bone marrow stromal cells, either bind to Wnt ligands directly or block Wnt receptors and co-receptors to halt Wnt-mediated signal transduction in both osteolineage and hematopoietic cell types. Secreted frizzled related proteins-1 and -2, Wnt inhibitory factor-1, Dickkopf-1, and Sclerostin are Wnt antagonists that influence hematopoietic cell fate decisions in the bone marrow niche. In this review, we compare and contrast the roles of these Wnt antagonists and their effects on hematopoietic development in mice, and also discuss the clinical significance of targeting Wnt antagonists within the context of hematopoietic disease.
authors.affiliation: Quantitative and Systems Biology Graduate Program, School of Natural Sciences, University of California, Merced, CA 95343, USA.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Cain
authors.forename: Jennifer O
authors.initials: JO
authors.lastname: Manilay
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D005819:Genetic Markers / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000502:physiology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D000099274:Frizzled-Related Proteins; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D002118:Calcium; D005819:Genetic Markers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins; C501126:DKK1 protein, human; C497573:LEF1 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C422903:SOST protein, human