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Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids
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Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids
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Journal Article
Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids
2016
Overview
The development of
in vitro
culture systems quantitatively and qualitatively recapitulating normal breast biology is key to the understanding of mammary gland biology. Current three-dimensional mammary culture systems have not demonstrated concurrent proliferation and functional differentiation
ex vivo
in any system for longer than 2 weeks. Here, we identify conditions including Neuregulin1 and R-spondin 1, allowing maintenance and expansion of mammary organoids for 2.5 months in culture. The organoids comprise distinct basal and luminal compartments complete with functional steroid receptors and stem/progenitor cells able to reconstitute a complete mammary gland
in vivo.
Alternative conditions are also described that promote enrichment of basal cells organized into multiple layers surrounding a keratinous core, reminiscent of structures observed in MMTV-Wnt1 tumours. These conditions comprise a unique tool that should further understanding of normal mammary gland development, the molecular mechanism of hormone action and signalling events whose deregulation leads to breast tumourigenesis.
Three-dimensional culture systems and organoids for mammary glands are important to understand mammary gland development. Here, the authors identify conditions (including Neuregulin 1 and R-spondin 1) that allow the culture of organoids that are responsive to hormonal stimulation for up to 2.5 months.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/51
/ 96/63
/ Animals
/ Biology
/ Female
/ Gene Expression Regulation, Developmental
/ Humanities and Social Sciences
/ Keratin
/ Mammary Glands, Animal - growth & development
/ Mammary Glands, Animal - metabolism
/ Organoids - growth & development
/ Prostate
/ Receptor, ErbB-3 - metabolism
/ Receptor, ErbB-4 - metabolism
/ Science
/ Steroids
/ Time-Lapse Imaging - methods
