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PMID: 20569694 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture.

Cell stem cell ·Vol. 6 ·No. 6 ·2010-06-04 ·Pages 568-77

Zeng YA, Nusse R

Abstract

Adult stem cells have the ability to self-renew and to generate specialized cells. Self-renewal is dependent on extrinsic niche factors but few of those signals have been identified. In addition, stem cells tend to differentiate in the absence of the proper signals and are therefore difficult to maintain in cell culture. The mammary gland provides an excellent system to study self-renewal signals, because the organ develops postnatally, arises from stem cells, and is readily generated from transplanted cells. We show here that adult mammary glands contain a Wnt-responsive cell population that is enriched for stem cells. In addition, stem cells mutant for the negative-feedback regulator Axin2 and therefore sensitized to Wnt signals have a competitive advantage in mammary gland reconstitution assays. In cell culture experiments, exposure to purified Wnt protein clonally expands mammary stem cells for many generations and maintains their ability to generate functional glands in transplantation assays. We conclude that Wnt proteins serve as rate-limiting self-renewal signals acting directly on mammary stem cells.

MeSH Terms
Adult Stem Cells/metabolism,pathology,transplantation Animals Axin Protein Cell Differentiation/genetics Cell Proliferation Cell Survival/genetics Cells, Cultured Cytoskeletal Proteins/genetics,metabolism Epithelial Cells/metabolism,pathology,transplantation Female Luciferases/genetics Mammary Glands, Animal/embryology,pathology Mice Mice, Inbred C57BL Mice, Mutant Strains Mice, Nude Mice, Transgenic Stem Cell Transplantation Wnt Proteins/genetics,metabolism Wnt3 Protein
Chemicals
Axin Protein Axin2 protein, mouse Cytoskeletal Proteins Wnt Proteins Wnt3 Protein Luciferases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zeng Yi Arial
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, School of Medicine, Stanford, CA 94305-5323, USA.
Nusse Roel
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1875-9777
DOI
10.1016/j.stem.2010.03.020
Published
2010-06-04
Pages
568-77
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC2917779
Subset
IM
Grants
Howard Hughes Medical Institute · United States
Corrections
CommentIn
PMID: 20569681
External Links
PubMed source DOI: 10.1016/j.stem.2010.03.020 PMC Full Text View journal details
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