Constitutive Notch2 signaling in neural stem cells promotes tumorigenic features and astroglial lineage entry.

Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural stem cells (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown to promote proliferation and tumorigenesis in GSCs. Notch2 is highly expressed in glioblastoma multiforme (GBM), a highly malignant astrocytoma. It is therefore conceivable that increased Notch2 signaling in NSCs contributes to the formation of GBM. Here, we demonstrate that mice constitutively expressing the activated intracellular domain of Notch2 in NSCs display a hyperplasia of the neurogenic niche and reduced neuronal lineage entry. Neurospheres derived from these mice show increased proliferation, survival and resistance to apoptosis. Moreover, they preferentially differentiate into astrocytes, which are the characteristic cellular population of astrocytoma. Likewise, we show that Notch2 signaling increases proliferation and resistance to apoptosis in human GBM cell lines. Gene expression profiling of GBM patient tumor samples reveals a positive correlation of Notch2 transcripts with gene transcripts controlling anti-apoptotic processes, stemness and astrocyte fate, and a negative correlation with gene transcripts controlling proapoptotic processes and oligodendrocyte fate. Our data show that Notch2 signaling in NSCs produces features of GSCs and induces astrocytic lineage entry, consistent with a possible role in astrocytoma formation.

Strain and high temperature superconductivity: unexpected results from direct electronic structure measurements in thin films.

Angle-resolved photoemission spectroscopy reveals very surprising strain-induced effects on the electronic band dispersion of epitaxial La(2-x)Sr(x)CuO(4-delta) thin films. In strained films we measure a band that crosses the Fermi level (E(F)) well before the Brillouin zone boundary. This is in contrast to the flat band reported in unstrained single crystals and in our unstrained films, as well as in contrast to the band flattening predicted by band structure calculations for in-plane compressive strain. In spite of the density of states reduction near E(F), the critical temperature increases in strained films with respect to unstrained samples. These results require a radical departure from commonly accepted notions about strain effects on high temperature superconductors, with possible general repercussions on superconductivity theory.