Mammary Epithelial Cell Lineage Analysis via the Lyon's Hypothesis

Implants of mammary glands from a single mammary fat pad in a H253 transgenic female mouse heterozygous for a lacZ-labeled X chromosome were analyzed at various time points following transplantation into the epithelium-cleared mammary fat pads of immune-compromised mice. The results show that the lacZ-marked X chromosome, demonstrated by nuclear-associated X-gal staining, was confined to a single epithelial clone that gave rise to the cap cells of all growing terminal end buds (TEB) in the expanding mammary outgrowths and also the basal cells of the elongated ducts. The nuclei of luminal cells in these ducts were uniformly negative for lacZ expression indicating that they were derived from cellular precursors that contained a silenced lac-Z marked X chromosome. This observation confirms the earlier work of Williams and Daniel, who concluded that cap cells were the precursors of the basal (myoepithelial cells) of the subtending mammary ducts.