Anti-LY6A monoclonal antibody, clone D7 [R-PE]

Stem cell antigen (Sca)-1/Ly6A, a glycerophosphatidylinositol-linked surface protein, was found to be associated with murine stem cell-and progenitor cell-enriched populations, and also has been linked to the capacity of tumor-initiating cells. Despite these interesting associations, this protein's functional role in these processes remains largely unknown. To identify the mechanism underlying the protein's possible role in mammary tumorigenesis, Sca-1 expression was examined in Sca-1(+/EGFP) mice during carcinogenesis. Mammary tumor cells derived from these mice readily engrafted in syngeneic mice, and tumor growth was markedly inhibited on down-regulation of Sca-1 expression. The latter effect was associated with significantly elevated expression of the TGF-beta ligand growth differentiation factor-10 (GDF10), which was found to selectively activate TGF-beta receptor (T beta RI/II)-dependent Smad3 phosphorylation. Overexpression of GDF10 attenuated tumor formation; conversely, silencing of GDF10 expression reversed these effects. Sca-1 attenuated GDF10-dependent TGF-beta signaling by disrupting the heterodimerization of T beta RI and T beta RII receptors. These findings suggest a new functional role for Sca-1 in maintaining tumorigenicity, in part by acting as a potent suppressor of TGF-beta signaling.

BACKGROUND: The adult mammalian heart displays a cardiomyocyte turnover rate of approximate to 1%/y throughout postnatal life and after injuries such as myocardial infarction (MI), but the question of which cell types drive this low level of new cardiomyocyte formation remains contentious. Cardiac resident stem cells marked by stem cell antigen -1 (Sca-1, gene name Ly6a) have been proposed as an important source of cardiomyocyte renewal. However, the in vivo contribution of endogenous Sca-1(+) cells to the heart at baseline or after MI has not been investigated. METHODS: Here we generated Ly6a gene targeted mice containing either a constitutive or an inducible Cre recombinase to perform genetic lineage tracing of Sca-1(+) cells in vivo. RESULTS: We observed that the contribution of endogenous Sca-1(+) cells to the cardiomyocyte population in the heart was <0.005% throughout all of cardiac development, with aging, or after MI. In contrast, Sca-1(+) cells abundantly contributed to the cardiac vasculature in mice during physiological growth and in the post -MI heart during cardiac remodeling. Specifically, Sca-1 lineage -traced endothelial cells expanded postnatally in the mouse heart after birth and into adulthood. Moreover, pulse labeling of Sca-1(+) cells with an inducible Ly6a-MerCreMer allele also revealed a preferential expansion of Sca-1 lineage -traced endothelial cells after MI injury in the mouse. CONCLUSIONS: Cardiac -resident Sca-1 cells are not significant contributors to cardiomyocyte renewal in vivo. However, cardiac Sca1(+) cells represent a subset of vascular endothelial cells that expand postnatally with enhanced responsiveness to pathological stress in vivo.