In situ identification of bipotent stem cells in the mammary gland.
The mammary epithelium undergoes profound morphogenetic changes during development. Architecturally, it comprises two primary lineages, the inner luminal and outer myoepithelial cell layers. Two opposing concepts on the nature of mammary stem cells (MaSCs) in the postnatal gland have emerged. One model, based on classical transplantation assays, postulates that bipotent MaSCs have a key role in coordinating ductal epithelial expansion and maintenance in the adult gland, whereas the second model proposes that only unipotent MaSCs identified by lineage tracing contribute to these processes. Through clonal cell-fate mapping studies using a stochastic multicolour cre reporter combined with a new three-dimensional imaging strategy, we provide evidence for the existence of bipotent MaSCs as well as distinct long-lived progenitor cells. The cellular dynamics at different developmental stages support a model in which both stem and progenitor cells drive morphogenesis during puberty, whereas bipotent MaSCs coordinate ductal homeostasis and remodelling of the mouse adult gland.
1] Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia [3].
Anne C
AC
Rios
1] Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia [3].
Nai Yang
NY
Fu
1] Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medicine, The University of Melbourne, Parkville, Victoria 3010, Australia [3] Department of Medical Oncology and Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Geoffrey J
GJ
Lindeman
1] Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Jane E
JE
Visvader
D000818:Animals; D019070:Cell Lineage; D058948:Cell Tracking; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D053547:Keratin-14 / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology*; D042361:Mammary Glands, Human / Q000166:cytology*; D051379:Mice; D009024:Morphogenesis; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011627:Puberty; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012741:Sexual Maturation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C500759:Elf5 protein, mouse; D053547:Keratin-14; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors