Fig. 3.

The mammary stem cell state is dynamic and context dependent. a Recent work has revealed that detectable MRU activity increases dramatically as the context of the fetal mammary epithelium changes in late gestation. b Candidate molecular regulators of the mammary stem cell state have been identified from molecular profiling of the late fetal mammary epithelium and associated stroma, but very few of these (bold) have been functionally and quantitatively tested for a role in mammary stem cell regulation. An emerging view is that when cells with intrinsic mammary stem cell potential (yellow cells) encounter appropriate microenvironmental stimuli (glowing cells) in the late stage embryo, they acquire properties that confer on them a stem cell state that can be expressed in isolation (ii). This does not occur at an earlier developmental stage either because critical response components or extrinsic stimulators are lacking (i), nor later under homeostatic conditions when more progeny become committed to specific lineages (green and red) (iii). The acquisition of an active stem state may also involve stimulation of non-stem cells in the niche (blue cells). Importantly, such molecular regulators may provide therapeutic targets if cancers achieve their robust stem like proliferative potential by resurrecting aspects of the fetal context