Journal
PHYSIOLOGICAL REVIEWS
Volume 100, Issue 2, Pages 489-523Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physrev.00040.2018
Keywords
breast cancer; mammary gland development; progenitors; stem cells; transcriptional regulators
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Funding
- Cancer Council Victoria Scholarship
- Cancer Therapeutics CRC Top-Up Scholarship
- National Breast Cancer Foundation/Cure Cancer Australia Fellowship
- Duke-NUS Faculty Start-up Fund
- National Health and Medical Research Council (NHMRC) [1078730]
- NHMRC Elizabeth Blackburn Research Fellowship [1102742]
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The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within the epithelial hierarchy. While unipotent progenitor cells predominantly execute day-to-day homeostasis and postnatal morphogenesis during puberty and pregnancy, multipotent MaSCs have been implicated in coordinating alveologenesis and long-term ductal maintenance. Nonetheless, the multipotency of stem cells in the adult remains controversial. The advent of large-scale single-cell molecular profiling has revealed striking changes in the gene expression landscape through ontogeny and the presence of transient intermediate populations. An increasing number of lineage cell-fate determination factors and potential niche regulators have now been mapped along the hierarchy, with many implicated in breast carcinogenesis. The emerging diversity among stem and progenitor populations of the mammary epithelium is likely to underpin the heterogeneity that characterizes breast cancer.
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