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

TY - JOUR

T1 - Multiscale imaging of basal cell dynamics in the functionally mature mammary gland

AU - Stevenson, Alexander J.

AU - Vanwalleghem, Gilles

AU - Stewart, Teneale A.

AU - Condon, Nicholas D.

AU - Lloyd-Lewis, Bethan

AU - Marino, Natascia

AU - Putney, James W.

AU - Scott, Ethan K.

AU - Ewing, Adam D.

AU - Davis, Felicity M.

PY - 2020/10/27

Y1 - 2020/10/27

N2 - 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 Ca 2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca 2+-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.

AB - 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 Ca 2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca 2+-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.

KW - Calcium signaling

KW - GCaMP6

KW - Lactation

KW - Mammary gland

KW - Oxytocin

KW - Mammary Glands, Human/metabolism

KW - Humans

KW - Mice, Transgenic

KW - Epithelial Cells/physiology

KW - Myosin Light Chains/metabolism

KW - Mammary Glands, Animal/cytology

KW - Animals

KW - Milk Ejection

KW - Mice

KW - Calcium Signaling

KW - Intravital Microscopy

U2 - 10.1073/pnas.2016905117

DO - 10.1073/pnas.2016905117

M3 - Journal article

C2 - 33033227

SN - 0027-8424

VL - 117

SP - 26822

EP - 26832

JO - Proceedings of the National Academy of Sciences (PNAS)

JF - Proceedings of the National Academy of Sciences (PNAS)

IS - 43

ER -