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: Veronica Rodilla, Alessandro Dasti, Mathilde Huyghe, Daniel Lafkas, Cécile Laurent, Fabien Reyal, Silvia Fre
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-02-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.1002069
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author Veronica Rodilla
Alessandro Dasti
Mathilde Huyghe
Daniel Lafkas
Cécile Laurent
Fabien Reyal
Silvia Fre
author_facet Veronica Rodilla
Alessandro Dasti
Mathilde Huyghe
Daniel Lafkas
Cécile Laurent
Fabien Reyal
Silvia Fre
author_sort Veronica Rodilla
collection DOAJ
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.
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spelling doaj.art-a333b8c4e955418ea7792308068241bd2022-12-21T22:40:36ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852015-02-01132e100206910.1371/journal.pbio.1002069Luminal progenitors restrict their lineage potential during mammary gland development.Veronica RodillaAlessandro DastiMathilde HuygheDaniel LafkasCécile LaurentFabien ReyalSilvia FreThe 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.https://doi.org/10.1371/journal.pbio.1002069
spellingShingle Veronica Rodilla
Alessandro Dasti
Mathilde Huyghe
Daniel Lafkas
Cécile Laurent
Fabien Reyal
Silvia Fre
Luminal progenitors restrict their lineage potential during mammary gland development.
PLoS Biology
title 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_short Luminal progenitors restrict their lineage potential during mammary gland development.
title_sort luminal progenitors restrict their lineage potential during mammary gland development
url https://doi.org/10.1371/journal.pbio.1002069
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