Project description:Autism spectrum disorder (ASD) manifests early in childhood. While genetic variants increase risk for ASD, a growing body of literature has established that in utero chemical exposures also contribute to ASD risk. These chemicals include air-based pollutants like diesel particulate matter (DPM). A combination of single-cell and direct transcriptomics of DPM-exposed human-induced pluripotent stem cell-derived cerebral organoids revealed toxicogenomic effects of DPM exposure during fetal brain development. Direct transcriptomics, sequencing RNA bases via Nanopore, revealed that cerebral organoids contain extensive RNA modifications, with DPM-altering cytosine methylation in oxidative mitochondrial transcripts expressed in outer radial glia cells. Single-cell transcriptomics further confirmed an oxidative phosphorylation change in cell groups such as outer radial glia upon DPM exposure. This approach highlights how DPM exposure perturbs normal mitochondrial function and cellular respiration during early brain development, which may contribute to developmental disorders like ASD by altering neurodevelopment.
Project description:Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.
Project description:A comprehensive cellular anatomy of normal human kidney is crucial to address the cellular origins of renal disease and renal cancer. Some kidney diseases may be cell type-specific, especially renal tubular cells. To investigate the classification and transcriptomic information of the human kidney, we rapidly obtained a single-cell suspension of the kidney and conducted single-cell RNA sequencing (scRNA-seq). Here, we present the scRNA-seq data of 23,366 high-quality cells from the kidneys of three human donors. In this dataset, we show 10 clusters of normal human renal cells. Due to the high quality of single-cell transcriptomic information, proximal tubule (PT) cells were classified into three subtypes and collecting ducts cells into two subtypes. Collectively, our data provide a reliable reference for studies on renal cell biology and kidney disease.
Project description:Total RNA sequecing for human induced pluripotent derived cerebral organoids from healthy controls and schizophrenia (SCZ) patients
Project description:Gene expression regulatory mechanisms in models of middle cerebral artery occlusion (MCAO) have been assessed in some studies, but questions remain. The discovery of differentially expressed genes (DEGs) between MCAO and control rats analyzed by next-generation RNA sequencing is of particular interest. These DEGs may help guide the clinical diagnosis of stroke and facilitate selection of the optimal treatment strategy. Twenty rats were equally divided into control and MCAO groups. Three rats from each group were randomly selected for RNA sequencing analysis. Sequence reads were obtained from an Illumina HiSeq2500 platform and mapped onto the rat reference genome RN6 using Hisat2. We identified 1,007 significantly DEGs with p<0.05, including 785 upregulated (fold change [FC]>2) and 222 downregulated (FC<0.5) DEGs, in brain tissue from MCAO rats compared with that from control rats, and numerous immune response genes were identified. Gene ontology (GO) analysis revealed that the majority of the most enriched and meaningful biological process terms were mainly involved in immune response, inflammatory response, cell activation, leukocyte migration, cell adhesion, response to external stimulus, cell migration, and response to wounding. Also enriched were immune-related pathways and neural-related pathways. Similar to GO molecular function terms, the enriched terms were mainly related to cytokine receptor activity. Six DEGs were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction analysis of these hits revealed that MCAO affects complement and coagulation cascades and chemokine signaling pathway. Our study identified novel biomarkers that could help further elucidate MCAO mechanisms and processes.