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Evidence for a stem cell hierarchy in the adult human breast
被引:292
作者:
Villadsen, Rene
Fridriksdottir, Agla J.
Ronnov-Jessen, Lone
Gudjonsson, Thorarinn
Rank, Fritz
LaBarge, Mark A.
Bissell, Mina J.
Petersen, Ole W.
[1
]
机构:
[1] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, DK-2200 Copenhagen N, Denmark
[2] Univ Copenhagen, Zoophysiol Lab, Dept Mol Biol, DK-2200 Copenhagen, Denmark
[3] Univ Iceland, Fac Med, Iceland Canc Soc, Mol & Cell Biol Res Lab, IS-125 Reykjavik, Iceland
[4] State Univ Hosp, Dept Pathol, DK-2100 Copenhagen O, Denmark
[5] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
关键词:
-;
D O I:
10.1083/jcb.200611114
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
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.
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页码:87 / 101
页数:15
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