Identity and dynamics of mammary stem cells during branching morphogenesis Journal Article

Author(s): Scheele, Colinda L; Hannezo, Edouard; Muraro, Mauro J; Zomer, Anoek; Langedijk, Nathalia S; Van Oudenaarden, Alexander; Simons, Benjamin D; Van Rheenen, Jacco
Article Title: Identity and dynamics of mammary stem cells during branching morphogenesis
Abstract: 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. Here we show that morphogenesis is driven by proliferative terminal end buds that terminate or bifurcate with near equal probability, in a stochastic and time-invariant manner, leading to a heterogeneous epithelial network. We 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. Our 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.
Journal Title: Nature
Volume: 542
Issue 7641
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2017-02-16
Start Page: 313
End Page: 317
DOI: 10.1038/nature21046
Notes: This work was supported by the European Research Council (consolidator grant 648804 to J.v.R.), the Worldwide Cancer Research (grant 13-0297 to J.v.R), and the Wellcome Trust (grant 098357/Z/12/Z to B.D.S. and 110326/Z/15/Z to E.H.). E.H. is funded by a Junior Research Fellowship from Trinity College, Cambridge, and a Sir Henry Wellcome Fellowship from the Wellcome Trust and acknowledges the Bettencourt-Schueller Young Researcher Prize for support. C.L.G.J.S. is funded by a Boehringer Ingelheim Fonds PhD Fellowship.
Open access: no