Mammary stem cells have myoepithelial cell properties

Abstract

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy.

Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

“…Contrary to predictions from the literature and the progenitor potential of myoepithelial cells in other organs, we found no evidence for the capacity of the myoepithelial lineage to contribute to other epithelial lineages in adult lacrimal glands (Makarenkova and Dartt, 2015;Prater et al, 2014;Zoukhri et al, 2007Zoukhri et al, , 2008. Rather, the maintenance of labeled cells after extensive chasing suggested that myoepithelial cells replenish themselves.…”

“…Previous studies have implicated myoepithelial cells as epithelial progenitors, but genetic lineage tracing of these cells has not been reported (Makarenkova and Dartt, 2015;Prater et al, 2014;Zoukhri et al, 2008). We genetically labeled myoepithelial cells in adult RFP reporter mice using the Acta2…”

The WNT-controlled transcriptional regulator LBH is required for mammary stem cell expansion and maintenance of the basal lineage

“…Lineage-tracing studies in mice have confirmed the existence of bi-potent basal MaSCs in the mammary gland in situ (Rios et al, 2014;van Amerongen et al, 2012), as well as identified lineagerestricted unipotent luminal and basal stem/progenitor cells (van Amerongen et al, 2012;Van Keymeulen et al, 2011), which likely together drive postnatal mammary gland morphogenesis in a dynamic fashion (Rios et al, 2014;van Amerongen et al, 2012). Moreover, in vitro and in vivo functional studies suggest that differentiated luminal and myoepithelial cells possess a remarkable plasticity and can dedifferentiate into basal MaSCs (Chaffer et al, 2011;Prater et al, 2014). However, the molecular mechanisms governing MaSC regulation in vivo remain ill defined.…”

Mammary gland development: cell fate specification, stem cells and the microenvironment

“…For example, the use of matrigel to prevent anoikis, and the injection of epithelia in their native configuration with attached stroma, both strongly increased gland reconstitution efficiency (Spike et al, 2012). Likewise, the culture of myoepithelial cells for one week in vitro was sufficient to massively increase MRU activity (Prater et al, 2014). Given these many potential variables, a consensus technical paper, comparing leading separation methods and providing guidance for future studies, has been published (Smalley et al, 2012).…”

“…2). Nonetheless, recent work suggests that the cells isolated via the sorting approach described above are all myoepithelial: myoepithelial cells expressing smooth muscle actin were the only cells able to repopulate the gland in one recent study (Prater et al, 2014). FACS and gland reconstitution from 8-12-week-old mice (in 50% matrigel)…”