Evidence for a stem cell hierarchy in the adult human breast
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Evidence for a stem cell hierarchy in the adult human breast. / Villadsen, René; Fridriksdottir, Agla J; Rønnov-Jessen, Lone; Gudjonsson, Thorarinn; Rank, Fritz; LaBarge, Mark A; Bissell, Mina J; Petersen, Ole W.
In: Journal of Cell Biology, Vol. 177, No. 1, 2007, p. 87-101.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Evidence for a stem cell hierarchy in the adult human breast
AU - Villadsen, René
AU - Fridriksdottir, Agla J
AU - Rønnov-Jessen, Lone
AU - Gudjonsson, Thorarinn
AU - Rank, Fritz
AU - LaBarge, Mark A
AU - Bissell, Mina J
AU - Petersen, Ole W
N1 - Keywords: Biological Markers; Breast; Cell Differentiation; Cell Line; Cell Lineage; Female; Humans; Keratins; Mammary Glands, Human; Oncogene Proteins, Viral; Repressor Proteins; Stem Cells; Transduction, Genetic
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1083/jcb.200611114
DO - 10.1083/jcb.200611114
M3 - Journal article
C2 - 17420292
VL - 177
SP - 87
EP - 101
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 1
ER -
ID: 9537911