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High Levels of Canonical Wnt Signaling Lead to Loss of Stemness and Increased Differentiation in Hematopoietic Stem Cells.
Famili, Farbod; Brugman, Martijn H; Taskesen, Erdogan; Naber, Brigitta E A; Fodde, Riccardo; Staal, Frank J T.
Afiliación
  • Famili F; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 Leiden, the Netherlands.
  • Brugman MH; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 Leiden, the Netherlands.
  • Taskesen E; Department of Clinical Genetics, VU University, 1081 Amsterdam, the Netherlands.
  • Naber BEA; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 Leiden, the Netherlands.
  • Fodde R; Department of Pathology, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
  • Staal FJT; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 Leiden, the Netherlands. Electronic address: f.j.t.staal@lumc.nl.
Stem Cell Reports ; 6(5): 652-659, 2016 05 10.
Article en En | MEDLINE | ID: mdl-27167156
Canonical Wnt signaling regulates the self-renewal of most if not all stem cell systems. In the blood system, the role of Wnt signaling has been the subject of much debate but there is consensus that high Wnt signals lead to loss of reconstituting capacity. To better understand this phenomenon, we have taken advantage of a series of hypomorphic mutant Apc alleles resulting in a broad range of Wnt dosages in hematopoietic stem cells (HSCs) and performed whole-genome gene expression analyses. Gene expression profiling and functional studies show that HSCs with APC mutations lead to high Wnt levels, enhanced differentiation, and diminished proliferation but have no effect on apoptosis, collectively leading to loss of stemness. Thus, we provide mechanistic insight into the role of APC mutations and Wnt signaling in HSC biology. As Wnt signals are explored in various in vivo and ex vivo expansion protocols for HSCs, our findings also have clinical ramifications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Diferenciación Celular / Regulación del Desarrollo de la Expresión Génica / Proteína de la Poliposis Adenomatosa del Colon Tipo de estudio: Guideline Límite: Animals Idioma: En Revista: Stem Cell Reports Año: 2016 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Diferenciación Celular / Regulación del Desarrollo de la Expresión Génica / Proteína de la Poliposis Adenomatosa del Colon Tipo de estudio: Guideline Límite: Animals Idioma: En Revista: Stem Cell Reports Año: 2016 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos