title: Wnt3a nanodisks promote ex vivo expansion of hematopoietic stem and progenitor cells.
abstract: BACKGROUND
  Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound palmitoleoyl moiety in the N-terminal domain.
  
  
  RESULTS
  By combining murine Wnt3a with phospholipid and apolipoprotein A-I, ternary complexes termed nanodisks (ND) were generated. ND-associated Wnt3a is soluble in the absence of detergent micelles and gel filtration chromatography revealed that Wnt3a co-elutes with ND. In signaling assays, Wnt3a ND induced β-catenin stabilization in mouse fibroblasts as well as hematopoietic stem and progenitor cells (HSPC). Prolonged exposure of HSPC to Wnt3a ND stimulated proliferation and expansion of Lin(-) Sca-1(+) c-Kit(+) cells. Surprisingly, ND lacking Wnt3a contributed to Lin(-) Sca-1(+) c-Kit(+) cell expansion, an effect that was not mediated through β-catenin.
  
  
  CONCLUSIONS
  The data indicate Wnt3a ND constitute a water-soluble transport vehicle capable of promoting ex vivo expansion of HSPC.
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.|Department of Hematology/Oncology, UCSF Benioff Children's Hospital Oakland, 747 52nd Street, Oakland, CA, 94609, USA.
authors.forename: Nahal R
authors.initials: NR
authors.lastname: Lalefar
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Witkowski
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.|Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Jens B
authors.initials: JB
authors.lastname: Simonsen
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA. rryan@chori.org.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004330:Drosophila; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D060509:Wnt3A Protein / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016632:Apolipoprotein A-I; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse
keywords: Hematopoietic stem and progenitor cell; Lipid-modified proteins; Murine Wnt3a; Nanodisk; Reconstituted high-density lipoprotein; β-Catenin