Hubrecht researchers show in a new Nature publication for the first time how healthy breast tissue is shaped by a heterogeneous pool of stem cells
During puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. The work of the groups of Jacco van Rheenen and Alexander van Oudenaarden, together with the research group of Simons in Cambridge now show that morphogenesis is driven by proliferative terminal end buds (see image below) that terminate or bifurcate with near equal probability, in a stochastic and time-invariant manner, leading to a heterogeneous epithelial network.
The researchers show that the majority of terminal end bud cells function as highly proliferative, lineage-committed MaSCs that are heterogeneous in their expression profile and short-term contribution to ductal extension. Yet, through cell rearrangements during terminal end bud bifurcation, each MaSC is able to contribute actively to long-term growth. In other words: the mammary stem cells shuffle their position randomly, so that they become functionally equal.The study shows that the behaviour of MaSCs is not directly linked to a single expression profile. Instead, morphogenesis relies upon lineage-restricted heterogeneous MaSC populations that function as single equipotent pools in the long term.
This is the first time that the identity of mammary stem cells and their role in the development of healthy breast tissue is described in great detail. And visualized: with the use of intravital imaging it was possible for the researchers to precisely track the individual stem cells in living mice. Knowing how healthy tissue develops is also an important step in understanding what happens in breast cancer cells.
Click on this link to read the whole paper at the Nature website.