Abstract
The hierarchical relationships between various stem and progenitor cell subpopulations driving mammary gland morphogenesis and homoeostasis are poorly understood. Conditional inactivation experiments previously demonstrated that expression of the zinc finger transcriptional repressor Blimp1/PRDM1 is essential for the establishment of epithelial cell polarity and functional maturation of alveolar cells. Here we exploit a Prdm1.CreERT2-LacZ reporter allele for lineage tracing experiments. Blimp1 expression marks a rare subpopulation of unipotent luminal stem cells that initially appear in the embryonic mammary gland at around E17.5 coincident with the segregation of the luminal and basal compartments. Fate mapping at multiple time points in combination with whole-mount confocal imaging revealed these long-lived unipotent luminal stem cells survive consecutive involutions and retain their identity throughout adult life. Blimp1+ luminal stem cells give rise to Blimp1− progeny that are invariably Elf5+ERα−PR−. Thus, Blimp1 expression defines a mammary stem cell subpopulation with unique functional characteristics.
Highlights
The hierarchical relationships between various stem and progenitor cell subpopulations driving mammary gland morphogenesis and homoeostasis are poorly understood
The functional relationships and behavioural dynamics of various stem and progenitor cell populations that contribute to mammary gland development and tissue homoeostasis remain poorly understood[1, 19]
Multipotent stem cells are known to be present at embryonic stages[4, 10, 13, 41], including a sub-population that remains bipotent in the postnatal mammary gland[5, 13]
Summary
The hierarchical relationships between various stem and progenitor cell subpopulations driving mammary gland morphogenesis and homoeostasis are poorly understood. Blimp[1] expression marks a rare subpopulation of unipotent luminal stem cells that initially appear in the embryonic mammary gland at around E17.5 coincident with the segregation of the luminal and basal compartments. We recently identified a rare subset of Blimp1-expressing luminal cells in the postnatal mammary gland. We demonstrate that Blimp1+ cells, initially detectable at embryonic (E) E17.5 in mammary rudiments, represent lineage-restricted, unipotent luminal progenitors that invariably lack ERα and PR expression. While Blimp1+ cells represent a very rare subset of luminal progenitors they display high self-renewal capacity, and contribute extensively to duct formation and homoeostasis, and to alveologenesis during pregnancy. The present experiments demonstrate that Blimp[1] expression marks a unipotent luminal stem cell population that substantially contributes to mammary gland morphogenesis throughout adult life
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
