Transcriptome Analysis of Ciliary-Dependent MCH Signaling in Differentiating 3T3-L1 Preadipocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE145452 | GEO | 2021/03/01
REPOSITORIES: GEO
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Project description:Transcriptome Analysis of Ciliary-Dependent MCH Signaling in Differentiating 3T3-L1 Preadipocytes
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Project description:Orexin/hypocretin receptor type 2 (Ox2R), which is widely expressed in the brain, receives orexin signals and modulates sleep and metabolism. Ox2R selective agonists are currently under clinical trials for narcolepsy treatment. Nevertheless, it remains unclear whether Ox2R exerts an inhibitory effect via Gi proteins in addition to an excitatory effect via Gq proteins. Here, we focused on Ox2R expression and function in MCH neurons, which have opposite roles to orexin neurons in sleep and metabolism regulation. Ox2R-expressing MCH neurons showed heterogeneity of RNA expression, and orexin B application in brain slices induced both excitatory and inhibitory responses in distinct MCH neuron populations. Ox2R inactivation in MCH neurons reduced transitions from NREM to REM sleep and impaired insulin sensitivity with hyperphagia. In conclusion, Ox2R mediates excitatory and inhibitory responses in MCH neuron subpopulations in vivo, which might regulate sleep and metabolism.
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Project description:In order to understand heterogeneity of MCH neurons, by using MCH-Cre dependent ZsGreen (fl/fl) reporter mice, we isolated nuclear from 16 hypothalami of 16 mice at the age of 16-18weeks. Through flow cytometry, we were able to distinguish ZsGreen positive nuclei, and collected puried MCH nuclei in suspension. Those nuclei suspension were subjected to single cell sequence by 10x™ GemCode™ Technology for further single nuleus mRNA analysis and unravel subclusters of MCH neurons
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Project description:We report phosphoRiboTrap experiments result which aim to explore the nature of the cell types in the Median Eminence (ME) regulated as a consequene of chemogenetic MCH neuron activation. Control and MCH-hM3Dq mice were 12 hrs-fasted and i.p. injected with CNO (3 mg/kg), Arcuate (ARC) and median eminence expat were extracted for preciptation of S6-marked ribosomes from both groups of mice. Extracted RNA from Immunoprecipitated ribosomes (IP) and total tissue (ARC+ME) from each mouse were subjected to deep mRNA sequencing. By analyzing the overlap of genes enriched in the IP/Input of MCH neuron activated mice with previously identified cell types using single cell mRNA sequencing of cells in the mediobasal hypothalamus (Campbell et al., 2017), we identified gene clusters which were activated upon MCH neuron activation.
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Project description:LEP-MCH conditioned childhood obesity
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Project description:In Alzheimer’s disease (AD), pathophysiological changes in the hippocampus cause deficits in episodic memory formation, leading to cognitive impairment. Hippocampal hyperactivity and decreased sleep quality are associated with early AD, but their basis is poorly understood. We find that homeostatic mechanisms transiently counteract increased excitatory drive of hippocampal CA1 neurons in AppNL-G-F mice, but fail to stabilize it at control levels. Spatial transcriptomics (ST) analysis identifies the Pmch gene encoding Melanin-Concentrating Hormone (MCH) as part of the adaptive response in AppNL-G-F mice. Hypothalamic MCH peptide is produced in sleep-active lateral hypothalamic neurons that project to CA1 and modulate memory. We show that MCH downregulates synaptic transmission and modulates firing rate homeostasis in hippocampal neurons. Moreover, MCH reverses the increased excitatory drive of CA1 neurons in AppNL-G-F mice. Consistent with our finding that a reduced fraction of MCH-neurons is active in AppNL-G-F mice, these animals spend less time in rapid eye movement (REM) sleep. In addition, MCH-axons projecting to CA1 become progressively impaired in both AppNL-G-F mice and AD patients. Our findings identify the MCH-system as vulnerable in early AD and suggest that impaired MCH-system function contributes to aberrant excitatory drive and sleep defects, which can compromise hippocampal-dependent functions.
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Project description:SGBS cells were used as a model system to investigate the cellular mode of action of a variety of plasticizers in human adipocytes. In brief, cells were cultured at 5% CO2 and 37°C in 95% humidity. Cells of generation 40 and passage 3 after thawing were grown to confluence with DMEM/F12 containing 33 µM biotin, 17 µM pantothenate, 100 U/l penicillin, and 0.1 mg/l streptomycin (basal medium) supplemented with 10% FCS (Gibco, Carlsbad, CA, USA). According to the standard differentiation protocol, differentiation was initiated (day 0) after changing to serum-free basal medium supplemented with 0.1 μM cortisol, 0.01 mg/ml apo-transferrin, 0.2 nM triiodothyronine, and 20 nM human insulin (differentiation medium) with the addition of 2 µM rosiglitazone, 25 nM dexamethasone, and 200 µM 3-isobutyl-1-methylxanthine for the first four days. The positive control was differentiated using the standard protocol with rosiglitazone. For plasticizer treatments, differentiation was conducted without rosiglitazone and cells were continuously exposed from day 0 – day 16 to the plasticizers or their transformation products. As for plasticizer treatments, the negative control was differentiated with rosiglitazone-free medium containing equivalent amounts of solvent (0.01 MeOH, v/v) for 16 days, resulting in minimal differentiation. All media were renewed every second day to mimic continuous exposure.
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Project description:Obesity is often associated with a low-grade systemic inflammation state that contributes to the development of insulin resistance and atherosclerotic complications. This is usually coupled with increased macrophage infiltration in the adipose tissue and a defect in adipocyte differentiation that results in accumulation of hypertrophic fat cells characterized by a deregulated pattern of adipokine expression. Here we show that knockdown of histone demethylase lsd1 in 3T3-L1 preadipocytes results in defective adipogenesis and derepression of an inflammatory program in these cells. The dataset consists of four sample groups: [1] 3T3-L1 preadipocytes (passage 19) transfected with a control scrambled siRNA at 24h after transfection (siC.24h), [2] 3T3-L1 preadipocytes (p.19) transfected with a siRNA directed against LSD1 at 24h after transfection (siLsd1.24h), [3] 3T3-L1 preadipocytes (p.21) transfected with a control scrambled siRNA at 48h after transfection (siC.48h), and [4] 3T3-L1 preadipocytes (p.21) transfected with a siRNA directed against LSD1 at 48h after transfection (siLsd1.48h). The 24h sample groups (siC.24h and siLsd1.24h) consist of two biological replicate samples; the 48h sample groups (siC.48h and siLsd1.48h) consist of three biological replicate samples. Each sample was hybridized to a separate array, for a total of ten arrays.
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