scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy

Targeting oncogenic pathways holds promise for brain tumor treatment, but inhibition of Sonic Hedgehog (SHH) signaling has failed in SHH-driven medulloblastoma. Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq and lineage tracing, we analyzed cellular diversity in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib. In untreated tumors, we find expected stromal cells and tumor-derived cells showing either a spectrum of neural progenitor-differentiation states or glial and stem cell markers. Vismodegib reduces the proliferative population and increases differentiation. However, specific cell types in vismodegib-treated tumors remain proliferative, showing either persistent SHH-pathway activation or stem cell characteristics. Our data show that even in tumors with a single pathway-activating mutation, diverse mechanisms drive tumor growth. This diversity confers early resistance to targeted inhibitor therapy, demonstrating the need to target multiple pathways simultaneously

Photon beam asymmetry Sigma for eta and eta ' photoproduction from the proton

Measurements of the linearly-polarized photon beam asymmetry $\Sigma$ for photoproduction from the proton of $\eta$ and $\eta^\prime$ mesons are reported. A linearly-polarized tagged photon beam produced by coherent bremsstrahlung was incident on a cryogenic hydrogen target within the CEBAF Large Acceptance Spectrometer. Results are presented for the $\gamma p \to \eta p$ reaction for incident photon energies from 1.070 to 1.876 GeV, and from 1.516 to 1.836 GeV for the $\gamma p \to \eta^\prime p$ reaction. For $\gamma p \to \eta p$, the data reported here considerably extend the range of measurements to higher energies, and are consistent with the few previously published measurements for this observable near threshold. For $\gamma p \to \eta^\prime p$, the results obtained are consistent with the few previously published measurements for this observable near threshold, but also greatly expand the incident photon energy coverage for that reaction. Initial analysis of the data reported here with the Bonn-Gatchina model strengthens the evidence for four nucleon resonances -- the $N(1895)1/2^-$, $N(1900)3/2^+$, $N(2100)1/2^+$ and $N(2120)3/2^-$ resonances -- which presently lack the "four-star" status in the current Particle Data Group compilation, providing examples of how these new measurements help refine models of the photoproduction process.Comment: 10 pages, 3 figure

Semi-inclusive pi(0) target and beam-target asymmetries from 6 GeV electron scattering with CLAS

We present precision measurements of the target and beam-target spin asymmetries from neutral pion electroproduction in deep-inelastic scattering (DIS) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. We scattered 6-GeV, longitudinally polarized electrons off longitudinally polarized protons in a cryogenic $^{14}$NH$_3$ target, and extracted double and single target spin asymmetries for $ep\rightarrow e^\prime\pi^0X$ in multidimensional bins in four-momentum transfer ($1.0<Q^2<3.2$ GeV$^2$), Bjorken-$x$ ($0.12<x<0.48$), hadron energy fraction ($0.4<z<0.7$), transverse pion momentum ($0<P_T<1.0$ GeV), and azimuthal angle $\phi_h$ between the lepton scattering and hadron production planes. We extracted asymmetries as a function of both $x$ and $P_T$, which provide access to transverse-momentum distributions of longitudinally polarized quarks. The double spin asymmetries depend weakly on $P_T$. The $\sin 2\phi_h$ moments are zero within uncertainties, which is consistent with the expected suppression of the Collins fragmentation function. The observed $\sin\phi_h$ moments suggest that quark gluon correlations are significant at large $x$.Comment: 18 preprint pages, 3 figure