期刊
CELL REPORTS
卷 18, 期 12, 页码 2825-2835出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.02.071
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资金
- Einstein Cancer Center [P30 CA013330]
- New York State Department of Health (NYSTEM Program) [C029154]
- NYSTEM [C028109, C029571]
- Susan Komen for the Cure [CCR12224440]
- V Foundation for Cancer Research
- Training Program in Cellular and Molecular Biology [2T32GM007491]
- Genetics and NYSTEM [C30392GG]
Delineating the mammary differentiation hierarchy is important for the study of mammary gland development and tumorigenesis. Mammary luminal cells are considered a major origin of human breast cancers. However, how estrogen-receptor-positive (ER+) and ER- luminal cells are developed and maintained remains poorly understood. The prevailing model suggests that a common stem/progenitor cell generates both cell types. Through genetic lineage tracing in mice, we find that SOX9-expressing cells specifically contribute to the development and maintenance of ER- luminal cells and, to a lesser degree, basal cells. In parallel, PROM1-expressing cells give rise only to ER+ luminal cells. Both SOX9(+) and PROM1(+) cells specifically sustain their respective lineages even after pregnancy-caused tissue remodeling or serial transplantation, demonstrating characteristic properties of long-term repopulating stem cells. Thus, our data reveal that mouse mammary ER+ and ER- luminal cells are two independent lineages that are maintained by distinct stem cells, providing a revised mammary epithelial cell hierarchy.
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