Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used th...

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Main Authors: Rodilla, Veronica, Dasti, Alessandro, Huyghe, Mathilde, Lafkas, Daniel, Laurent, Cécile, Reyal, Fabien, Fre, Silvia
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331521/
id pubmed-4331521
recordtype oai_dc
spelling pubmed-43315212015-02-24 Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development Rodilla, Veronica Dasti, Alessandro Huyghe, Mathilde Lafkas, Daniel Laurent, Cécile Reyal, Fabien Fre, Silvia Research Article The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. Public Library of Science 2015-02-17 /pmc/articles/PMC4331521/ /pubmed/25688859 http://dx.doi.org/10.1371/journal.pbio.1002069 Text en © 2015 Rodilla et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Rodilla, Veronica
Dasti, Alessandro
Huyghe, Mathilde
Lafkas, Daniel
Laurent, Cécile
Reyal, Fabien
Fre, Silvia
spellingShingle Rodilla, Veronica
Dasti, Alessandro
Huyghe, Mathilde
Lafkas, Daniel
Laurent, Cécile
Reyal, Fabien
Fre, Silvia
Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development
author_facet Rodilla, Veronica
Dasti, Alessandro
Huyghe, Mathilde
Lafkas, Daniel
Laurent, Cécile
Reyal, Fabien
Fre, Silvia
author_sort Rodilla, Veronica
title Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development
title_short Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development
title_full Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development
title_fullStr Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development
title_full_unstemmed Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development
title_sort luminal progenitors restrict their lineage potential during mammary gland development
description The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331521/
_version_ 1613189394799263744

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