Multiscale imaging of basal cell dynamics in the functionally mature mammary gland

The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of mil...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-10, Vol.117 (43), p.26822-26832
Main Authors: Stevenson, Alexander J., Vanwalleghem, Gilles, Stewart, Teneale A., Condon, Nicholas D., Lloyd-Lewis, Bethan, Marino, Natascia, Putney, James W., Scott, Ethan K., Ewing, Adam D., Davis, Felicity M.
Format: Article
Language:English
Subjects:
Alveoli
Animals
Biological Sciences
Blood volume
Calcium ions
Calcium Signaling
Calcium signalling
Contractility
Epithelial cells
Epithelial Cells - physiology
Epithelium
Humans
Intravital Microscopy
Mammary gland
Mammary glands
Mammary Glands, Animal - cytology
Mammary Glands, Animal - diagnostic imaging
Mammary Glands, Animal - physiology
Mammary Glands, Human - metabolism
Mice
Mice, Transgenic
Milk
Milk Ejection
Myosin Light Chains - metabolism
Oscillations
Transgenic mice
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Summary:The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network. Using quantitative, multidimensional imaging of mammary cell ensembles from GCaMP6 transgenic mice, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk begins its passage toward the dependent neonate, seconds after the command.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2016905117