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Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation (ChIP-Seq)

ABSTRACT: To profile Sox2 and Sox9 binding sites in Gq-DREADD expressing CNO treated brains in comparison to control. Furthermore, we also aimed to profile Sox9 binding sites in odor treated vs. control olfactory bulbs. An additional goal of this study was to profile histone serotonylation mark in Slc22a3-cKO olfactory bulb in comparison to control.

ORGANISM(S): Mus musculus

PROVIDER: GSE229644 | GEO | 2023/04/17

REPOSITORIES: GEO

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Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation (RNA-Seq)

Project description:To profile gene expression differences in astrocytes after chemogenetic neuronal activation in different mouse brain regions. Furthermore, we also sought to profile gene expression differences between control and Slc22a3 conditional knockout astrocytes in the mouse olfactory bulb.

2023-04-17 | GSE229641 | GEO

Astrocyte Gi signaling activation in the striatum

Project description:The Khakh laboratory used astrocyte selective AAVs expressing Rpl22-HA and hM4Di, a Gi DREADD, in the striatum. Mice recieved either 1 mg/kg CNO or vehicle to compare striatal astrocyte transcriptomes with and without Gi-GPCR signaling activation.

2019-08-30 | GSE119058 | GEO

Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses

Project description:G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest. We show that the chimeric DREADD-β2AR triggers responses comparable to levalbuterol-stimulated β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in primary microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we utilized the microglia-like HMC3 cell line and included two additionally designed DREADD-based chimeras mimicking GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A had no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands.

2022-07-06 | GSE194125 | GEO

Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome [RNA-seq]

Project description:Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in which 5-HT can be added to histone proteins to regulate transcription, a process called H3 serotonylation. Here, we show that H3 serotonylation undergoes dynamic regulation during placental development, corresponding to gene expression changes that are known to influence key metabolic processes. Using transgenic mice, we demonstrate that placental H3 serotonylation largely depends on 5-HT uptake by the serotonin transporter (Sert/Slc6a4). Sert deletion robustly reduces enrichment of H3 serotonylation across the placental genome, and disrupts neurodevelopmental gene networks in offspring brain tissues. Thus, these findings suggest a novel role for H3 serotonylation in coordinating placental transcription at the intersection of maternal physiology and offspring brain development.

2024-01-23 | GSE246539 | GEO

Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome [ChIP-seq]

2024-01-23 | GSE246538 | GEO

Chemogenetic activation of astrocytes in the hippocampus and cortex changes the transcriptome of microglia

Project description:Astrocytes are the most common glial cell type in the brain, yet, it is still not clear how their activation affects the transcriptome of neighboring microglia and neurons. Engineered G protein-coupled receptors (GPCRs) called Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) make it possible to selectively activate specific cell types, such as neurons and astrocytes. By combining the selective activation of astrocytes with single cell RNA sequencing, we were able to study transcriptional changes that occur in response to the activation of astrocytes at the single cell level. Interestingly, our data shows that long-term activation of astrocytes in healthy mice results in dramatic alteration in the transcriptome of astrocytes and microglia. Genes that were differentially expressed in these Gq-DREADD-activated astrocytes were involved in neurogenesis and low-density lipoprotein particle biology, while those in the microglia were involved in lipoprotein handling, purinergic receptor activity, and immune cell migration and chemotaxis. Furthermore, network analysis showed that Gq-DREADD-mediated activation in astrocytes resulted in an upregulation of genes involved in the GPCR signaling pathways and calcium ion homeostasis, confirming astrocyte activation through Gq-DREADD expression. Our findings show the importance of considering transcriptomic alterations in microglia after the activation of astrocytes in in vivo models. Therefore, our data will serve as a resource for the broader neuroscience community.

2023-07-09 | GSE154208 | GEO

5HT - Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3

Project description:we provide evidence for a new class of histone posttranslational modification (PTM): serotonylation.

2018-12-19 | PXD008106 | Pride

Olfactory proteomics in Dementia with Lewy bodies

Project description:Proteomic analysis were performed in olfactory bulbs derived from controls and individuals with dementia with lewy bodies

2021-09-08 | PXD016069 | Pride

Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development [RNA-seq 2]

Project description:Purpose: To asses changes in gene expression profiles from the P30 wild type littermate control olfactory bulbs and conditional double knockout olfactory bulbs of hGFAP-Cre; Sp8 Flox/Flox; Sp9 Flox/Flox mice. Methods: Total RNA was isolated and sequenced from the olfactory bulbs of the P30 wild type littermate controls or hGFAP-Cre; Sp8 Flox/Flox; Sp9 Flox/Flox mice in tetrad using an illumina high-seq 2500. Raw data was analyzed using TopHat. Genes were considered changed which performed fold-change>=2 and FDR<=0.05. Changed genes were then filtered to reveal the downstream targets of Sp8 and Sp9. Results: 31 genes were significantly increased and 74 genes were significantly decreased in expression level due to the loss of Sp9 and Sp8 expression.

2017-01-04 | GSE93061 | GEO

Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development [RNA-Seq]

Project description:Purpose: To asses changes in gene expression profiles from the P11 no cre littermate control olfactory bulbs and conditional double knockout olfactory bulbs of Dlx5/6-CIE; Sp8 Flox/Flox; Sp9 Flox/Flox (Sp8/Sp9-DCKO) mice. Methods: Total RNA was isolated and sequenced from the olfactory bulbs of the P11 no cre littermate controls or Sp8/Sp9-DCKO mice in duplicate using an illumina high-seq 2500. Raw data was analyzed using TopHat. Genes were considered changed which performed fold-change>=2 and FDR<=0.05. Changed genes were then filtered to reveal the downstream targets of Sp8 and Sp9. Results: 32 genes were significantly increased and 144 genes were significantly decreased in expression level due to the loss of Sp9 and Sp8 expression.

2016-09-03 | GSE86396 | GEO

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