Identification of stem cell units in the terminal end bud and duct of the mouse mammary gland

Abstract

The mouse mammary gland may undergo cycles of proliferation, terminal differentiation, tissue remodeling, and more importantlymalignant transformation.Mammary epithelial stem cells and their progeny participate in these processes.Mammary epithelial stemcells are multipotent, exhibit properties of self renewal (up to 7 divisions)and may exist either as long-lived nondividing cells or asproliferating-differentiating cells. The focus of this study was to locate stem cells by identifying them as long-lived, label-retainingmammary epithelial cells (LRCs)in growth active (developing)or growth static (aged)mammar y ducts. Initially, primary epithelialcells were pulse labeled with either fluorescent tracker dye and/or BrdU. Cells were then transplanted into cleared juvenile syngeneicmammary fat pads and held for 5weeks or 8weeks. In this study, we demonstrate that LRCs are stem cells and their progeny(transitional cells)ar e arranged as transitional units (TUs). Additionally, TUs are located every 250 ± 75 νm in ducts or in theterminal end bud 200-600 νm in diameter. Molecules expressed in TUs were Zonula Occludens-1 and α-catenin proteins whichwere significantly detected in 75%-91% (P < 0.001)of the LRCs cells that make up the TU. These data suggest that transitionalunits may be a group of label-retaining stem cells and maybe involved in the developmental or cancer process. © 2001 Hindawi Publishing Corporation.