Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

Introducing high school students to the Gene Ontology classification system.

We present an activity that introduces high school students to the Gene Ontology classification system which is widely used in genomics and systems biology studies to characterize large sets of genes based on functional and structural information. This is a valuable and standardized method used to identify genes that act in similar processes and pathways and also to gain insight into the overall architecture and distribution of genes and gene families associated with a particular tissue or disease. Through this exercise, students will learn how the classification system works by analyzing a list of genes using DAVID the Database for Annotation, Visualization and Integrated Discovery that incorporates the Gene Ontology system into its suite of analysis tools. This method of profiling genes is used by our high school student interns to categorize gene expression data related to behavioral neuroscience. Students will get a feel for working with genes and gene sets, gain vocabulary, obtain an understanding of how a database is structured and gain an awareness of the vast amount of information that is known about genes as well as the online analysis tools that are available.

Sex differences in gene expression patterns associated with the APOE4 allele.

Background: The APOE gene encodes apolipoprotein ε (ApoE), a protein that associates with lipids to form lipoproteins that package and traffic cholesterol and lipids through the bloodstream. There are at least three different alleles of the APOE gene: APOE2, APOE3, and APOE4. The APOE4 allele increases an individual's risk for developing late-onset Alzheimer disease (AD) in a dose-dependent manner. Sex differences have been reported for AD susceptibility, age of onset, and symptom progression, with females being more affected than males. Methods: In this study, we use a systems biology approach to examine gene expression patterns in the brains of aged female and male individuals who are positive for the APOE4 allele in order to identify possible sex-related differences that may be relevant to AD. Results: Based on correlation analysis, we identified a large number of genes with an expression pattern similar to that of APOE in APOE4-positive individuals. The number of these genes was much higher in APOE4-positive females than in APOE4-positive males, who in turn had more of such genes than APOE4-negative control groups. Our findings also indicate a significant sex* genotype interaction for the CNTNAP2 gene, a member of the neurexin family and a significant interaction for brain area*sex* genotype for PSEN2, a risk factor gene for AD.  Conclusions: Profiling of these genes using Gene Ontology (GO) term classification, pathway enrichment, and differential expression analysis supports the idea of a transcriptional role of APOE with respect to sex differences and AD.