Developmental Changes in the in Vitro Activated Regenerative Activity of Primitive Mammary Epithelial Cells

Maisam Makarem, Nagarajan Kannan, Long V. Nguyen, David J.H.F. Knapp, Sneha Balani, Michael D. Prater, John Stingl, Afshin Raouf, Oksana Nemirovsky, Peter Eirew, Connie J. Eaves

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Many normal adult tissues contain rare stem cells with extensive self-maintaining regenerative potential. During development, the stem cells of the hematopoietic and neural systems undergo intrinsically specified changes in their self-renewal potential. In the mouse, mammary stem cells with transplantable regenerative activity are first detectable a few days before birth. They share some phenotypic properties with their adult counterparts but are enriched in a subpopulation that displays a distinct gene expression profile. Here we show that fetal mammary epithelial cells have a greater direct and inducible growth potential than their adult counterparts. The latter feature is revealed in a novel culture system that enables large numbers of in vitro clonogenic progenitors as well as mammary stem cells with serially transplantable activity to be produced within 7 days from single fetal or adult input cells. We further show that these responses are highly dependent on novel factors produced by fibroblasts. These findings provide new avenues for elucidating mechanisms that regulate normal mammary epithelial stem cell properties at the single-cell level, how these change during development, and how their perturbation may contribute to transformation.

Original languageEnglish (US)
Article numbere1001630
JournalPLoS biology
Volume11
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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    Makarem, M., Kannan, N., Nguyen, L. V., Knapp, D. J. H. F., Balani, S., Prater, M. D., Stingl, J., Raouf, A., Nemirovsky, O., Eirew, P., & Eaves, C. J. (2013). Developmental Changes in the in Vitro Activated Regenerative Activity of Primitive Mammary Epithelial Cells. PLoS biology, 11(8), [e1001630]. https://doi.org/10.1371/journal.pbio.1001630