Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 14, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12951-016-0218-5
Keywords
Murine Wnt3a; Nanodisk; Reconstituted high-density lipoprotein; Hematopoietic stem and progenitor cell; beta-Catenin; Lipid-modified proteins
Funding
- Clinical Fellowship from California Institute of Regenerative Medicine [TG2-01164]
- Jordan Family Fund
- NIH [R37 HL64159, K18 HL102257]
- Danish Villum Kann Rasmussen Foundation
- Ib Mogens Kristiansen Almene Foundation
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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 beta-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 beta-catenin. Conclusions: The data indicate Wnt3a ND constitute a water-soluble transport vehicle capable of promoting ex vivo expansion of HSPC.
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