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Genes Dev. 2014 Jun 1;28(11):1143-58. doi: 10.1101/gad.242511.114.

Mammary stem cells and the differentiation hierarchy: current status and perspectives.

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Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville VIC 3010, Australia;
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom.


The mammary epithelium is highly responsive to local and systemic signals, which orchestrate morphogenesis of the ductal tree during puberty and pregnancy. Based on transplantation and lineage tracing studies, a hierarchy of stem and progenitor cells has been shown to exist among the mammary epithelium. Lineage tracing has highlighted the existence of bipotent mammary stem cells (MaSCs) in situ as well as long-lived unipotent cells that drive morphogenesis and homeostasis of the ductal tree. Moreover, there is accumulating evidence for a heterogeneous MaSC compartment comprising fetal MaSCs, slow-cycling cells, and both long-term and short-term repopulating cells. In parallel, diverse luminal progenitor subtypes have been identified in mouse and human mammary tissue. Elucidation of the normal cellular hierarchy is an important step toward understanding the "cells of origin" and molecular perturbations that drive breast cancer.


breast cancer; development; epigenome; lineage tracing; mammary stem cell; steroid hormone

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