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PMID: 17420292 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Evidence for a stem cell hierarchy in the adult human breast.

The Journal of cell biology ·Vol. 177 ·No. 1 ·2007-04-09 ·Pages 87-101

Villadsen R, Fridriksdottir AJ, Rønnov-Jessen L, Gudjonsson T, Rank F, LaBarge MA, Bissell MJ, Petersen OW

Abstract

Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially quiescent, whereas the progenitor cells in the lobules were more likely to be actively dividing. Cells from ducts and lobules collected under the microscope were functionally characterized by colony formation on tissue culture plastic, mammosphere formation in suspension culture, and morphogenesis in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites in situ confirmed this pattern. The proposal that the four cell types are indeed constituents of an as of yet undescribed stem cell hierarchy was assessed in long-term cultures in which senescence was bypassed. These findings identify an adult human breast ductal stem cell activity and its earliest descendants.

MeSH Terms
Biomarkers/metabolism Breast/cytology,metabolism Cell Differentiation Cell Line Cell Lineage Female Humans Keratins/metabolism Mammary Glands, Human/cytology Oncogene Proteins, Viral/genetics Papillomavirus E7 Proteins Repressor Proteins/genetics Stem Cells/classification,metabolism Transduction, Genetic
Chemicals
Biomarkers E6 protein, Human papillomavirus type 16 Oncogene Proteins, Viral Papillomavirus E7 Proteins Repressor Proteins oncogene protein E7, Human papillomavirus type 16 Keratins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Villadsen René
Department of Cellular and Molecular Medicine, Faculty of Health Sciences, and Zoophysiological Laboratory, University of Copenhagen, and Department of Pathology, State University Hospital, Copenhagen, Denmark.
Fridriksdottir Agla J
Rønnov-Jessen Lone
Gudjonsson Thorarinn
Rank Fritz
LaBarge Mark A
Bissell Mina J
Petersen Ole W
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200611114
Published
2007-04-09
Pages
87-101
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064114
Subset
IM
Grants
NCI NIH HHS · R01 CA064786 · United States
NCI NIH HHS · R37 CA064786 · United States
NCI NIH HHS · CA-64786 · United States
External Links
PubMed source DOI: 10.1083/jcb.200611114 PMC Full Text View journal details
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