Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage

Keymeulen, Alexandra Van; Fioramonti, Marco; Centonze, Alessia; Bouvencourt, Gaëlle; Achouri, Younès; Blanpain, Cédric

doi:10.1016/j.celrep.2017.07.066

Cited by 90 publications

(91 citation statements)

References 37 publications

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“…Lineage-tracing of the luminal cell population has revealed that ER + progeny are restricted to the ER + lineage and, likewise, ER− progeny are restricted to the ER− lineage during pregnancy, lactation and involution 15–17 . Furthermore, Wap-Cre, which is active only during pregnancy in the ER − alveolar cells, marked only ER − labeled cells after two pregnancies 18 .…”

Section: Mammary Epithelial Cells Have Limited Plasticity In Vivomentioning

confidence: 99%

Epithelial plasticity in the mammary gland

Seldin

Guelte

Macara

2017

Current Opinion in Cell Biology

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Many epithelial tissues rely on multipotent stem cells for the proper development and maintenance of their diverse cell lineages. Nevertheless, the identification of multipotent stem cell populations within the mammary gland has been a point of contention over the past decade. In this review, we provide a critical overview of the various lineage-tracing studies performed to address this issue and conclude that although multipotent stem cells exist in the embryonic mammary placode, the postnatal mammary gland instead contains distinct unipotent progenitor populations that contribute to stage-specific development and homeostasis. This begs the question of why differentiated mammary epithelial cells can exhibit stem cell behavior in culture, and we speculate that such reprogramming potential is repressed in situ under normal conditions but revealed in vitro and might drive breast cancer development.

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Section: Mammary Epithelial Cells Have Limited Plasticity In Vivomentioning

confidence: 99%

Epithelial plasticity in the mammary gland

Seldin

Guelte

Macara

2017

Current Opinion in Cell Biology

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“…The adult mammary epithelium consists of an arborized ductal network embedded within an adipose stroma (1). The ductal epithelium contains both luminal and basal cells, which are produced and maintained postnatally by lineage-restricted precursors (2)(3)(4)(5)(6)(7). During gestation, a coordinated program of epithelial proliferation, side-branching, differentiation and tissue remodeling takes place (1,8), resulting in the generation of thousands of alveolar structures that adorn the central ductal epithelium in lobular clusters (9).…”

Section: Introductionmentioning

confidence: 99%

Mammary mechanobiology: mechanically-activated ion channels in lactation and involution

Stewart

Hughes

Stevenson

et al. 2019

Preprint

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A mother's ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by secretory mammary epithelial cells is adaptive, its release is exquisitely timed and its own glandular stagnation with the permanent cessation of suckling triggers the programmed cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals control epithelial expansion, function and remodeling. Despite this duality of input, however, the nature and function of mechanical forces in the mammary gland remain unknown. Here, we characterize the mammary force landscape and the capacity of luminal and basal epithelial cells to Short title: The mechanics of milk production experience and exert force. We explore the molecular instruments for force-sensing in the mammary gland and the physiological requirement for PIEZO1 in lactation and involution. Our study supports the existence of a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.

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“…Recent lineage tracing studies from the Blanpain and Guo groups have identified potential ER-positive stem cells that can maintain the ER-positive lineage through multiple rounds of grafting! (Van Keymeulen et al, 2017;Wang et al, 2017). This ER-positive stem cell (marked "H" in Fig 1) is potentially the cell of origin of human luminal and molecular tumours.…”

Section: Introductionmentioning

confidence: 94%

Classification of breast tumours into molecular apocrine, luminal and basal groups based on an explicit biological model

Iggo

2018

Preprint

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The gene expression profiles of human breast tumours fall into three main groups that have been called luminal, basal and either HER2-enriched or molecular apocrine. To escape from the circularity of descriptive classifications based purely on gene signatures I describe a biological classification based on a model of the mammary lineage. In this model I propose that the third group is a tumour derived from a mammary hormone-sensing cell that has undergone apocrine metaplasia. I first split tumours into hormone sensing and milk secreting cells based on the expression of transcription factors linked to cell identity (the luminal progenitor split), then split the hormone sensing group into luminal and apocrine groups based on oestrogen receptor activity (the luminal-apocrine split). I show that the luminalapocrine-basal (LAB) approach can be applied to microarray data (186 tumours) from an EORTC trial and to RNA-seq data from TCGA (674 tumours), and compare results obtained with the LAB and PAM50 approaches. Unlike pure signature-based approaches, classification based on an explicit biological model has the advantage that it is both refutable and capable of meaningful improvement as biological understanding of mammary tumorigenesis improves.

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Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage

Cited by 90 publications

References 37 publications

Epithelial plasticity in the mammary gland

Epithelial plasticity in the mammary gland

Mammary mechanobiology: mechanically-activated ion channels in lactation and involution

Classification of breast tumours into molecular apocrine, luminal and basal groups based on an explicit biological model

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