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.
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW &University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Colinda L G J
authors.initials: CL
authors.lastname: Scheele
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK.|The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.|The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, UK.
authors.forename: Edouard
authors.initials: E
authors.lastname: Hannezo
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW &University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Mauro J
authors.initials: MJ
authors.lastname: Muraro
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW &University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Anoek
authors.initials: A
authors.lastname: Zomer
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW &University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Nathalia S M
authors.initials: NS
authors.lastname: Langedijk
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW &University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK.|The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.|The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, UK.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW &University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Jacco
authors.initials: J
authors.lastname: van Rheenen
mesh_terms: D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008958:Models, Molecular; D009024:Morphogenesis; D012741:Sexual Maturation; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013269:Stochastic Processes