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Rhodes, C. T.

Publications and source records attributed to Rhodes, C. T..

3 recordsLinked to original sources

Differential Gene Expression in MRI-classified Glioblastoma

Previous characterization of the genome and transcriptome of glioblastoma (GBM) has revealed molecular alterations that potentially drive GBM pathogenesis and heterogeneity 1-6. These open-resources are evolving, such as The Cancer Genome Atlas (TCGA) and The Cancer Imaging Atlas (TCIA) at the National Institute of Health comprising a large cohort of molecular and MRI data. Yet, no report deciphers the link between molecular signatures and MRI-classified GBM. The necessity to re-form molecular and imaging data motivated our computational approach to integrate TCIA and TCGA datasets derived from GBM. We uncovered common and distinct molecular signatures across GBM patients and specific to tumor locations, respectively. Despite heterogeneity in GBM, the top 12 genes from our analysis highlights that the dysregulation of a subset of neurotransmitter receptor or transporter and synaptic activity is common across GBM patients. The coherent layer of imaging and molecular information would help us stratify precision neuro-oncology and treatment options in ways that are not possible through MRI or genomic data alone. Our findings provide molecular targets in the disrupted neurocircuit of GBM, suggesting imbalanced excitation and inhibition. Given the fact that GBM patients exhibit similar symptoms resembling patients with neurodegenerative diseases and seizures, our results supported the hypothesis-GBM in the context of neurological disorders beyond a solely cancerous disease.

cancer biology↗

Loss of Ezh2 in the medial ganglionic eminence alters interneuron fate, cell morphology and gene expression profiles

Enhancer of zeste homolog 2 (Ezh2) is responsible for trimethylation of histone 3 at lysine 27 (H3K27me3), resulting in gene repression. Here, we explore the role of Ezh2 in forebrain GABAergic interneuron development. Loss of Ezh2 increases somatostatin-expressing (SST+) and decreases parvalbumin-expressing (PV+) interneurons in multiple brain regions. We also observe fewer MGE-derived interneurons in the first postnatal week, indicating reduced interneuron production. Intrinsic electrophysiological properties in SST+ and PV+ interneurons are normal, but PV+ interneurons display increased axonal complexity in Ezh2 mutant mice. Single cell multiome analysis revealed differential gene expression patterns in the embryonic MGE that are predictive of these cell fate changes. Lastly, CUT&Tag analysis revealed differential H3K27me3 levels at specific genomic loci, with some genes displaying a relative increase in H3K27me3 indicating they may be resistant to epigenetic modifications. Thus, loss of Ezh2 in the MGE alters interneuron fate, morphology, and gene expression and regulation.

neuroscience↗

Single cell chromatin accessibility reveals regulatory elements and developmental trajectories in the embryonic forebrain

A comprehensive characterization of epigemonic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. We collected single-cell chromatin accessibility profiles from four distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types or brain regions. We integrated snATAC-Seq and single cell transcriptome data to characterize changes of chromatin accessibility at enhancers and promoters with associated transcript abundance. Multi-modal integration of histone modifications (CUT&Tag and CUT&RUN), promoter-enhancer interactions (Capture-C) and high-order chromatin structure (Hi-C) extended these initial observations. This dataset reveals a diverse chromatin landscape with region-specific regulatory mechanisms and genomic interactions in distinct neurogenic regions of the embryonic mouse brain and represents an extensive public resource of a ground truth epigenomic landscape at this critical stage of neurogenesis.

neuroscience↗