s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue

Abstract

Mammary stem cells (MaSCs) play critical roles in normal development and perhaps tumorigenesis of the mammary gland. Using combined cell markers, adult MaSCs have been enriched in a basal cell population, but the exact identity of MaSCs remains unknown. We used the s-SHIP promoter to tag presumptive stem cells with GFP in the embryos of a transgenic mouse model. Here we show, in postnatal mammary gland development, that GFP [Keywords: Stem cell; mammary gland development; cap cells; alveolar bud cells; s-SHIP; breast tumors] Supplemental material is available at http://www.genesdev.org.

From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

“…Similar results were also obtained when the Wnt receptor LPR5 was deleted [23]. A recent study showed that using a GFP reporter driven by the s-SHIP promoter, GFP + replicating "active" MaSCs can be identified in cap cells in puberty and basal alveolar bud cells in pregnancy, but not in adult virgin animals, or in mammary tissues during lactation or involution stages [16]. Future characterizations will help to better understand whether or not distinct MaSC populations exist, and how they are controlled by their local micro-environmental cues.…”

“…The peak of this expansion seems to occur mid-to late-pregnancy at the end of alveolar proliferation and the onset of differentiation to begin milk production. Although s-SHIP promoter-driven GFP reporter marks active MaSCs in both the puberty and pregnancy stages [16], it is unknown whether pregnancyassociated MaSCs come from the same stem cell population important for pubertal growth, or if a distinct MaSC population exists or is responsible specifically for growth during pregnancy. While the start of milk production corresponds with the drop in MaSC numbers, sustained milk production continues to affect the rate of MaSC apoptosis, as when mothers do not nurse their young MaSC numbers drop quicker than those who do nurse their young [22].…”

“…Sca1 + cells were shown to be a subpopulation of the label-retaining epithelial cells, and when isolated they showed a degree of in vivo reconstitution ability. However, subsequent studies would identify markers which could enrich for MaSCs to a much higher degree of purity, and MaSCs identified by other methods have been shown to be Sca1 low/- [7,16].…”

Adult Gland Derived Stem Cells (Gdscs); Potentials, Hurdles and Expectations

“…Another study showed that with the use of a GFP reporter driven by the s-SHIP promoter, GFP+ replicating active MaSCs can be identified in cap cells at puberty and basal alveolar bud cells in pregnancy, but not in adult virgin animals, or in mammary tissues during lactation or involution stages [89].…”

Comparison of Genome Aberrations Between Early-Onset and Late-Onset Breast Cancer

“…The predominance of immature epithelial cells in embryo provides the target for the initiation of tumorigenesis when intrauterine hormone concentration is high. Indeed, animal studies showed that undifferentiated TEB is the most susceptible to carcinogen for the formation of tumor (Bai and Rohrschneider, 2010;Roussos et al, 2010;Russo and Russo, 1994). Recent evidence even points to the immature gland in utero as the target for the initiation of breast cancer (Brisken and O'Malley, 2010;Hardy et al, 2010;Hilakivi-Clarke and Clarke, 1998;Sanderson et al, 1998;Torres-Arzayus et al, 2010).…”