Essential role for a novel population of binucleated mammary epithelial cells in lactation.
The mammary gland represents a unique tissue to study organogenesis as it predominantly develops in the post-natal animal and undergoes dramatic morphogenetic changes during puberty and the reproductive cycle. The physiological function of the mammary gland is to produce milk to sustain the newborn. Here we view the lactating gland through three-dimensional confocal imaging of intact tissue. We observed that the majority of secretory alveolar cells are binucleated. These cells first arise in very late pregnancy due to failure of cytokinesis and are larger than mononucleated cells. Augmented expression of Aurora kinase-A and Polo-like kinase-1 at the lactogenic switch likely mediates the formation of binucleated cells. Our findings demonstrate an important physiological role for polyploid mammary epithelial cells in lactation, and based on their presence in five different species, suggest that binucleated cells evolved to maximize milk production and promote the survival of offspring across all mammalian species.
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Anne C
AC
Rios
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Nai Yang
NY
Fu
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Paul R
PR
Jamieson
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Bhupinder
B
Pal
Imaging Laboratory, Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Lachlan
http://orcid.org/0000-0002-4388-9642
L
Whitehead
Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
Kevin R
KR
Nicholas
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Familial Cancer Centre and Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.|Department of Medicine, The University of Melbourne, Parkville, Victoria 3010, Australia.
Geoffrey J
http://orcid.org/0000-0001-9386-2416
GJ
Lindeman
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Jane E
JE
Visvader
D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism; D001942:Breast Feeding; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000648:ultrastructure; D048429:Cell Size; D048749:Cytokinesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000648:ultrastructure; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C576917:AURKA protein, human