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Epithelial Progenitors in the Normal Human Mammary Gland

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Abstract

The human mammary gland is organized developmentally as a hierarchy of progenitor cells that become progressively restricted in their proliferative abilities and lineage options. Three types of human mammary epithelial cell progenitors are now identified. The first is thought to be a luminal-restricted progenitor; in vitro under conditions that support both luminal and myoepithelial cell differentiation, this cell produces clones of differentiating daughter cells that are exclusively positive for markers characteristic of luminal cells produced in vivo (i.e., keratins 8/18 and 19, epithelial cell adhesion molecule [EpCAM] and MUC1). The second type is a bipotent progenitor. It is identified by its ability to produce “mixed” colonies in single cell assays. These colonies contain a central core of cells expressing luminal markers surrounded by cells with a morphology and markers (e.g., keratin 14+) characteristic of myoepithelial cells. Serial passage in vitro of an enriched population of bipotent progenitors promotes the expansion of a third type of progenitor that is thought to be myoepithelial-restricted because it only produces cells with myoepithelial features. Luminal-restricted and bipotent progenitors can prospectively be isolated as distinct subpopulations from freshly dissociated suspensions of normal human mammary cells. Both are distinguished from many other cell types in mammary tissue by their expression of EpCAM and CD49f (α6 integrin). They are distinguished from each other by their differential expression of MUC1, which is expressed at much higher levels on the luminal progenitors. To relate the role of these progenitors to the generation of the three-dimensional tubuloalveolar structure of the mammary tree produced in vivo, we propose a model in which the commitment to the luminal versus the myoepithelial lineage may play a determining role in the generation of alveoli and ducts.

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Abbreviations

EpCAM:

epithelial cell adhesion molecule

TDLU:

terminal ductal lobular unit

TEB:

terminal end bud

SMA:

smooth muscle actin

SLC:

small light cell

K:

keratin

MaSC:

mammary stem cell

HMEC:

human mammary epithelial cell

Ma-CFC:

mammary colony-forming cell

Ma-CFCLu:

luminal-restricted progenitor

Ma-CFC-Me:

myoepithelialrestricted progenitor

Ma-CFC-LuMe:

bipotent progenitor

CALLA:

common acute lymphoblastic leukemia antigen

ESA:

epithelial specific antigen

BGA2:

histo-blood group antigen H type 2

EGF:

epidermal growth factor

FACS:

fluorescenceactivated cell sorting

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Authors and Affiliations

  1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

    John Stingl, Afshin Raouf & Connie J. Eaves

  2. StemCell Technologies Inc., Vancouver, British Columbia, Canada

    John Stingl

  3. Department of Anatomy and Cell Biology, University of British Columbia, Vancouver, British Columbia, Canada

    Joanne T. Emerman

  4. The Terry Fox Laboratory, 601 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada

    Connie J. Eaves

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  1. John Stingl
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Correspondence to Connie J. Eaves.

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Stingl, J., Raouf, A., Emerman, J.T. et al. Epithelial Progenitors in the Normal Human Mammary Gland. J Mammary Gland Biol Neoplasia 10, 49–59 (2005). https://doi.org/10.1007/s10911-005-2540-7

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