The identity of mammary stem and progenitor cells remains poorly
understood, mainly as a result of the lack of robust markers. The Notch
signaling pathway has been implicated in mammary gland development as
well as in tumorigenesis in this tissue. Elevated expression of the
Notch3 receptor has been correlated to the highly aggressive “triple
negative” human breast cancer. However, the specific cells expressing
this Notch paralogue in the mammary gland remain unknown. Using a
conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we
genetically marked Notch3-expressing cells throughout mammary gland
development and followed their lineage in vivo. We demonstrate that
Notch3 is expressed in a highly clonogenic and transiently quiescent
luminal progenitor population that gives rise to a ductal lineage. These
cells are capable of surviving multiple successive pregnancies,
suggesting a capacity to self-renew. Our results also uncover a role for
the Notch3 receptor in restricting the proliferation and consequent
clonal expansion of these cells