Anti-LY6A Monoclonal antibody, clone E8 [APC]

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.

Efficient delivery of gene therapy vectors across the blood-brain barrier (BBB) is the holy grail of neurological disease therapies. A variant of the neurotropic vector adeno-associated virus (AAV) serotype 9, called AAV-PHP.B, was shown to very efficiently deliver transgenes across the BBB in C57BL/6J mice. Based on our recent observation that this phenotype is mouse strain dependent, we used whole-exome sequencing-based genetics to map this phenotype to a specific haplotype of lymphocyte antigen 6 complex, locus A (Ly6a) (stem cell antigen-1 [Sca-1]), which encodes a glycosylphosphatidylinositol (GPI)-anchored protein whose function had been thought to be limited to the biology of hematopoiesis. Additional biochemical and genetic studies definitively linked high BBB transport to the binding of AAV-PHP.B with LY6A (SCA-1). These studies identify, for the first time, a ligand for this GPI-anchored protein and suggest a role for it in BBB transport that could be hijacked by viruses in natural infections or by gene therapy vectors to treat neurological diseases.