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Nat Cell Biol. 2018 Jun;20(6):666-676. doi: 10.1038/s41556-018-0095-2. Epub 2018 May 21.

Early lineage segregation of multipotent embryonic mammary gland progenitors.

Author information

1
Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium.
2
Department of Human Genetics, University of Leuven, KU Leuven, Leuven, Belgium.
3
Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, UK.
4
Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium. Cedric.Blanpain@ulb.ac.be.
5
Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Université Libre de Bruxelles (ULB), Brussels, Belgium. Cedric.Blanpain@ulb.ac.be.

Abstract

The mammary gland is composed of basal cells and luminal cells. It is generally believed that the mammary gland arises from embryonic multipotent progenitors, but it remains unclear when lineage restriction occurs and what mechanisms are responsible for the switch from multipotency to unipotency during its morphogenesis. Here, we perform multicolour lineage tracing and assess the fate of single progenitors, and demonstrate the existence of a developmental switch from multipotency to unipotency during embryonic mammary gland development. Molecular profiling and single cell RNA-seq revealed that embryonic multipotent progenitors express a unique hybrid basal and luminal signature and the factors associated with the different lineages. Sustained p63 expression in embryonic multipotent progenitors promotes unipotent basal cell fate and was sufficient to reprogram adult luminal cells into basal cells by promoting an intermediate hybrid multipotent-like state. Altogether, this study identifies the timing and the mechanisms mediating early lineage segregation of multipotent progenitors during mammary gland development.

PMID:
29784918
PMCID:
PMC5985933
DOI:
10.1038/s41556-018-0095-2
[Indexed for MEDLINE]
Free PMC Article

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