Evidence for a stem cell hierarchy in the adult human breast.
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.
Villadsen
René
R
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
AJ
Rønnov-Jessen
Lone
L
Gudjonsson
Thorarinn
T
Rank
Fritz
F
LaBarge
Mark A
MA
Bissell
Mina J
MJ
Petersen
Ole W
OW
D015415:Biomarkers / Q000378:metabolism; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D005260:Female; D006801:Humans; D007633:Keratins / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics; D013234:Stem Cells / Q000145:classification* / Q000378:metabolism; D014161:Transduction, Genetic
D015415:Biomarkers; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007633:Keratins