Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids

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<jats:title>Abstract</jats:title><jats:p>The development of <jats:italic>in vitro</jats:italic> 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 <jats:italic>ex vivo</jats:italic> 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 <jats:italic>in vivo.</jats:italic> 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.</jats:p>

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  • Nature Communications

    Nature Communications 7 (1), 13207-, 2016-10-26

    Springer Science and Business Media LLC

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