Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages.
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.
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Chunhui
C
Wang
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
John R
JR
Christin
Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467, USA; Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Maja H
MH
Oktay
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: wenjun.guo@einstein.yu.edu.
Wenjun
W
Guo
D000071916:AC133 Antigen / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D038081:Organogenesis; D011960:Receptors, Estrogen / Q000378:metabolism*; D012038:Regeneration; D055758:SOX9 Transcription Factor / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D000071916:AC133 Antigen; C000606024:Prom1 protein, mouse; D011960:Receptors, Estrogen; D055758:SOX9 Transcription Factor
breast cancer; cancer cell-of-origin; estrogen receptor negative cancer; estrogen receptor positive cancer; lineage tracing; mammary differentiation; mammary gland development; mammary gland regeneration; mammary stem cells; stem cell hierarchy