Tao, Luweivan Bragt, Maaike P.A.Li, Zhe2015-12-042015Tao, Luwei, Maaike P.A. van Bragt, and Zhe Li. 2015. “A Long-Lived Luminal Subpopulation Enriched with Alveolar Progenitors Serves as Cellular Origin of Heterogeneous Mammary Tumors.” Stem Cell Reports 5 (1): 60-74. doi:10.1016/j.stemcr.2015.05.014. http://dx.doi.org/10.1016/j.stemcr.2015.05.014.2213-6711http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845139Summary It has been shown that the mammary luminal lineage could be maintained by luminal stem cells or long-lived progenitors, but their identity and role in breast cancer remain largely elusive. By lineage analysis using Wap-Cre mice, we found that, in nulliparous females, mammary epithelial cells (MECs) genetically marked by Wap-Cre represented a subpopulation of CD61+ luminal progenitors independent of ovarian hormones for their maintenance. Using a pulse-chase lineage-tracing approach based on Wap-Cre adenovirus (Ad-Wap-Cre), we found that Ad-Wap-Cre-marked nulliparous MECs were enriched with CD61+ alveolar progenitors (APs) that gave rise to CD61− alveolar luminal cells during pregnancy/lactation and could maintain themselves long term. When transformed by different oncogenes, they could serve as cells of origin of heterogeneous mammary tumors. Thus, our study revealed a type of long-lived AP within the luminal lineage that may serve as the cellular origin of multiple breast cancer subtypes.en-USJournal Article2015-12-0410.1016/j.stemcr.2015.05.014