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


ABSTRACT: 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.

SUBMITTER: Jarde T 

PROVIDER: S-EPMC5095178 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Jardé Thierry T   Lloyd-Lewis Bethan B   Thomas Mairian M   Kendrick Howard H   Melchor Lorenzo L   Bougaret Lauriane L   Watson Peter D PD   Ewan Kenneth K   Smalley Matthew J MJ   Dale Trevor C TC  

Nature communications 20161026


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 or  ...[more]

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