Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential

Qiaoxiang Dong, Hui Gao, Yuanshuo Shi, Fuchuang Zhang, Xiang Gu, Anqi Wu, Danhan Wang, Yuanhong Chen, Abhik Bandyopadhyay, I. Tien Yeh, Benjamin J. Daniel, Yidong Chen, Yi Zou, Vivienne L. Rebel, Christi A Walter, Jianxin Lu, Changjiang Huang, Luzhe Sun

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Breast cancer incidence increases during aging, yet the mechanism of age-associated mammary tumorigenesis is unclear. Mammary stem cells are believed to play an important role in breast tumorigenesis, but how their function changes with age is unknown. We compared mammary epithelial cells isolated from young and old mammary glands of different cohorts of C57BL6/J and BALB/c mice, and our findings revealed that old mammary glands were characterized by increased basal cell pool comprised of mostly CD49fhi cells, altered luminal-to-basal cell ratio, and irregular ductal morphology. More interestingly, basal stem cells in old mice were increased in frequency, but showed a functional decline of differentiation and increased neoplastic transformation potential. Gene signature enrichment analysis revealed a significant enrichment of a luminal cell gene expression signature in the basal stem cell-enriched population from old mice, suggesting some luminal cells were expressing basal markers. Immunofluorescence staining confirmed the presence of luminal cells with high CD49f expression in hyperplastic lesions implicating these cells as undergoing luminal to basal phenotypic changes during aging. Whole transcriptome analysis showed elevated immune and inflammatory responses in old basal stem cells and stromal cells, which may be the underlying cause for increased CD49fhi basal-like cells in aged glands.

Original languageEnglish (US)
Pages (from-to)2754-2776
Number of pages23
JournalAging
Volume8
Issue number11
DOIs
StatePublished - 2016

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Keywords

  • Aging
  • Breast cancer
  • Mammary stem cell
  • Neoplasia

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Dong, Q., Gao, H., Shi, Y., Zhang, F., Gu, X., Wu, A., Wang, D., Chen, Y., Bandyopadhyay, A., Yeh, I. T., Daniel, B. J., Chen, Y., Zou, Y., Rebel, V. L., Walter, C. A., Lu, J., Huang, C., & Sun, L. (2016). Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential. Aging, 8(11), 2754-2776. https://doi.org/10.18632/aging.101082