CA2 Pyramidal Layer

This report contains a gene expression summary of the CA2 pyramidal cell layer (CA2sp), derived from the Allen Brain Atlas (ABA) in situ hybridization mouse data set. The structure's location and morphological characteristics in the mouse brain are described using the Nissl data found in the Allen Reference Atlas. Using an established algorithm, the expression values of the CA2sp were compared to the values of the macro/parent-structure, in this case the pyramidal layer of Ammon’s Horn, for the purpose of extracting regionally selective gene expression data. The genes with the highest ranking selectivity ratios were manually curated and verified. 50 genes were then selected and compiled for expression characterization. The experimental data for each gene may be accessed via the links provided; additional data in the sagittal plane may also be accessed using the ABA. Correlations between gene expression in the CA2sp and the rest of the brain, across all genes in the coronal dataset (~4300 genes), were derived computationally. A gene ontology table (derived from DAVID Bioinformatics Resources 2007) is also included, highlighting possible functions of the 50 genes selected for this report

Facial Motor Nucleus

This report contains a summary of expression patterns for genes that are enriched in the facial motor nucleus (VII) of the medulla. All data is derived from the Allen Brain Atlas (ABA) in situ hybridization mouse project. The structure's location and morphological characteristics in the mouse brain are described using the Nissl data found in the Allen Reference Atlas. Using an established algorithm, the expression values of the facial motor nucleus were compared to the values of its larger parent structure, in this case the medulla, for the purpose of extracting regionally selective gene expression data. The highest ranking genes were manually curated and verified. 50 genes were then selected and compiled for expression analysis. The experimental data for each gene may be accessed via the links provided; additional data in the sagittal plane may also be accessed using the ABA. Correlations between gene expression in the facial motor nucleus and the rest of the brain, across all genes in the coronal dataset (~4300 genes), were derived computationally. A gene ontology table (derived from DAVID Bioinformatics Resources 2007) is also included, highlighting possible functions of the 50 genes selected for this report

Dentate Gyrus

This report contains a gene expression summary of the dentate gyrus (DG), derived from the Allen Brain Atlas (ABA) _in situ_ hybridization mouse data set. The structure's location and morphological characteristics in the mouse brain are described using the Nissl data found in the Allen Reference Atlas. Using an established algorithm, the expression values of the dentate gyrus were compared to the values of the macro/parent-structure, in this case the hippocampal region, for the purpose of extracting regionally selective gene expression data. The genes with the highest ranking selectivity ratios were manually curated and verified. 50 genes were then selected and compiled for expression characterization. The experimental data for each gene may be accessed via the links provided; additional data in the sagittal plane may also be accessed using the ABA. Correlations between gene expression in the dentate gyrus and the rest of the brain, across all genes in the coronal dataset (~4300 genes), were derived computationally. A gene ontology table (derived from DAVID Bioinformatics Resources 2007) is also included, highlighting possible functions of the 50 genes selected for this report

Combating subclonal evolution of resistant cancer phenotypes

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves

Adult Spinal Cord Radial Glia Display a Unique Progenitor Phenotype

Radial glia (RG) are primarily embryonic neuroglial progenitors that express Brain Lipid Binding Protein (Blbp a.k.a. Fabp7) and Glial Fibrillary Acidic Protein (Gfap). We used these transcripts to demarcate the distribution of spinal cord radial glia (SCRG) and screen for SCRG gene expression in the Allen Spinal Cord Atlas (ASCA). We reveal that neonatal and adult SCRG are anchored in a non-ventricular niche at the spinal cord (SC) pial boundary, and express a “signature” subset of 122 genes, many of which are shared with “classic” neural stem cells (NSCs) of the subventricular zone (SVZ) and SC central canal (CC). A core expressed gene set shared between SCRG and progenitors of the SVZ and CC is particularly enriched in genes associated with human disease. Visualizing SCRG in a Fabp7-EGFP reporter mouse reveals an extensive population of SCRG that extend processes around the SC boundary and inwardly (through) the SC white matter (WM), whose abundance increases in a gradient from cervical to lumbar SC. Confocal analysis of multiple NSC-enriched proteins reveals that postnatal SCRG are a discrete and heterogeneous potential progenitor population that become activated by multiple SC lesions, and that CC progenitors are also more heterogeneous than previously appreciated. Gene ontology analysis highlights potentially unique regulatory pathways that may be further manipulated in SCRG to enhance repair in the context of injury and SC disease

The F0F1-ATP Synthase Complex Contains Novel Subunits and Is Essential for Procyclic Trypanosoma brucei

The mitochondrial F0F1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F0F1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F1 subunits, three to F0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F1 α subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage) cells and are important for the structural integrity of the F0F1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder