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30.01.17 Simons lab and colleagues identify stem cells that generate branching ducts in mammary gland

last modified Jan 30, 2017 05:17 PM
Nature paper describes how stem cell behaviour underlies branching morphogenesis in the mammary gland
30.01.17 Simons lab and colleagues identify stem cells that generate branching ducts in  mammary gland

Visualisation of branching network of mammary ductal epithelium in 8-week-old mouse.

Identity and dynamics of mammary stem cells during branching morphogenesis

Colinda L. G. J. Scheele, Edouard Hannezo, Mauro J. Muraro, Anoek Zomer, Nathalia S. M. Langedijk, Alexander van Oudenaarden, Benjamin D. Simons & Jacco van Rheenen (2017) Nature DOI: 10.1038/nature21046

[Advance Online Publication Monday 30 January 2017]

 

The Simons lab, with colleagues in Cambridge and the Netherlands, have pinpointed how stem cells produce the branched network of ducts in the [mouse] mammary gland. Owing to the absence of exclusive stem cell markers, little is known about how mammary stem cells (MaSCs) drive branching morphogenesis.

By combining genetic-lineage tracing and whole-gland mapping, the authors identify the location and number of MaSCs and define quantitatively how the fate of MaSCs translates into organ structure. They conclude “This study is notable as it emphasises that the behaviour and even the identity of stem cells cannot be linked directly to a single molecular profile or specific markers, but must be defined functionally.”

 

Abstract from the paper

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.

 

Read more about research in the Simons lab.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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