by Keyword: RNA seq

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Dhillon, Poonam, Park, Jihwan, Hurtado del Pozo, Carmen, Li, Lingzhi, Doke, Tomohito, Huang, Shizheng, Zhao, Juanjuan, Kang, Hyun Mi, Shrestra, Rojesh, Balzer, Michael S., Chatterjee, Shatakshee, Prado, Patricia, Han, Seung Yub, Liu, Hongbo, Sheng, Xin, Dierickx, Pieterjan, Batmanov, Kirill, Romero, Juan P., Prósper, Felipe, Li, Mingyao, Pei, Liming, Kim, Junhyong, Montserrat, Nuria, Susztak, Katalin, (2021). The nuclear receptor ESRRA protects from kidney disease by coupling metabolism and differentiation Cell Metabolism 33, (2), 379-394.E8

Kidney disease is poorly understood because of the organ’s cellular diversity. We used single-cell RNA sequencing not only in resolving differences in injured kidney tissue cellular composition but also in cell-type-specific gene expression in mouse models of kidney disease. This analysis highlighted major changes in cellular diversity in kidney disease, which markedly impacted whole-kidney transcriptomics outputs. Cell-type-specific differential expression analysis identified proximal tubule (PT) cells as the key vulnerable cell type. Through unbiased cell trajectory analyses, we show that PT cell differentiation is altered in kidney disease. Metabolism (fatty acid oxidation and oxidative phosphorylation) in PT cells showed the strongest and most reproducible association with PT cell differentiation and disease. Coupling of cell differentiation and the metabolism was established by nuclear receptors (estrogen-related receptor alpha [ESRRA] and peroxisomal proliferation-activated receptor alpha [PPARA]) that directly control metabolic and PT-cell-specific gene expression in mice and patient samples while protecting from kidney disease in the mouse model.

Keywords: Single-cell RNA sequencing, Single-cell ATAC sequencing, Kidney, Fibrosis, Organoids, Fatty-acid oxidation, PPARA, ESRRA, Proximal tubule cells, Chronic kidney disease

Tomas-Roig, J., Piscitelli, F., Gil, V., del Río, J. A., Moore, T. P., Agbemenyah, H., Salinas-Riester, G., Pommerenke, C., Lorenzen, S., Beißbarth, T., Hoyer-Fender, S., Di Marzo, V., Havemann-Reinecke, U., (2016). Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice Behavioural Brain Research , 303, 34-43

Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.

Keywords: Psychosocial stress, Cerebellum, Calreticulin, Endocannabinoid system, Behavior, RNA seq.