Project description:Here, we examined diversity in the cell-type composition of the mouse anterior thalamic nuclei (ATN) using single-cell RNA-seq and single-cell spatial transcriptomics.
Project description:We profiled the transcriptome of 22 thalamic nuclei. Nuclei were retrogradely labeled from their forebrain target areas, microdissected and fluorescent cells pooled. Anterograde tracing was used when identification of nuclear boundaries was ambiguous. We found that thalamic nuclei share a common axis of variance closely linked to the mediolateral spatial axis of thalamus. This axis was enriched in functionally relevant genes such as neurotransmitter receptors and ion channels, and was closely linked to functional and morphological properties of the neurons.
Project description:The thalamus is the principal information hub of the vertebrate brain, with essential roles in sensory and motor information processing, attention, and memory. The complex array of thalamic nuclei develops from a restricted pool of neural progenitors. We apply longitudinal single-cell RNA-sequencing and regional abrogation of Sonic hedgehog (Shh) to map the developmental trajectories of thalamic progenitors, intermediate progenitors, and post-mitotic neurons as they coalesce into distinct thalamic nuclei. These data reveal that the complex architecture of the thalamus is established early during embryonic brain development through the coordinated action of four cell differentiation lineages derived from Shh-dependent and independent progenitors. We systematically characterize the gene expression programs that define these thalamic lineages across time and demonstrate how their disruption upon Shh depletion causes pronounced locomotor impairment resembling infantile Parkinson’s disease. These results reveal key principles of thalamic development and provide mechanistic insights into neurodevelopmental disorders resulting from thalamic dysfunction.
Project description:We performed single nuclei and spatial transcriptomic sequencing on a cohort of solid tumor human brain metastasis specimens resected at Duke University Medical Center from 1998 to 2022. This includes 23 single nuclei specimens, 12 Visium standard specimens, and 4 Xenium specimens. These samples encompass metastases from lung cancer, breast cancer, melanoma, and sarcoma primaries. Analysis of these data revealed novel tumor-microenvironment cell-cell interactions associated with patient survival.
Project description:Obsessive-compulsive disorder (OCD) is a severe psychiatric illness associated with hyperactivity and hyperconnectivity in corticostriatalthalamocortical circuits of the prefrontal cortex. We previously identified dysregulated mRNA expression in the medial orbitofrontal cortex and striatum of subjects with OCD, affecting a wide range of processes and cell types. The purpose of this study was to examine OCD-related differential expression in the thalamus, using a postmortem cohort of 10 subjects with OCD and 11 unaffected comparison subjects. Tissue was collected from four higher-order thalamic nuclei: the mediodorsal magnocellular (MDmc), mediodorsal parvocellular (MDpc), ventral anterior (VA), and ventrolateral posterior (VLp) nuclei.