Single-cell Transcriptome Landscape and Cell Fate Decoding in Human Brain Organoids after Transplantation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE243015 | GEO | 2024/08/16
REPOSITORIES: GEO
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Project description:We performed high-throughput snRNA-seq on hippocampus (Hip) and prefrontal lobe cortex (PFC) tissue in mice (Mus musculus) to identify cell-type specific differentially expressed genes. Mice were divided into GF, SPF and CGF group.
2023-03-15 | GSE202704 | GEO
Project description:To identify gene expression changes associated with Crtc1 deficiency, we performed genome-wide transcriptome profile analyses by using mouse cDNA microarrays in the cortex of Crtc1â/â and WT female mice BACKGROUND: Recent studies involve the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brain of mood disorders patients. We showed that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate neurobehavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. METHODS: The molecular basis of the behavioral phenotype of Crtc1â/â mice was further examined using microarray analysis. We characterized Agmat expression in the prefrontal cortex (PFC) and hippocampus (HIP) by quantitative polymerase chain reaction (qPCR), Western blot (WB) analysis, and confocal immunofluorescence microscopy. The antidepressant effect of agmatine was assessed by the forced swim test (FST). Brain-derived neurotrophic factor (BDNF) levels and eukaryotic elongation factor 2 (eEF2) phosphorylation were measured by WB. RESULTS: Microarray, qPCR and WB analyses revealed an upregulation of Agmat in Crtc1â/â PFC and HIP, where immunofluorescence microscopy showed more Agmat-expressing cells, notably parvalbumin- and somatostatin-interneurons. Acute agmatine treatment efficiently improved depressive-like behavior of Crtc1â/â mice in the FST, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit induced by upregulated Agmat. In WT mice, agmatine rapidly increased BDNF levels and eEF2 dephosphorylation, indicating that it might be a fastâacting antidepressant with NMDA receptor antagonist properties. CONCLUSIONS: Collectively, these findings support the involvement of the agmatinergic system in the depressive-like phenotype of Crtc1â/â mice, and allow a better understanding of the agmatinergic system and its putative role in major depression. RNA from cortex of 5 WT and 5 KO mice was used
2016-07-18 | E-GEOD-80633 | biostudies-arrayexpress
Project description:Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (~16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100 % in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the â??switchesâ?? of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects.
2009-06-22 | E-TABM-718 | biostudies-arrayexpress
Project description:Aims: To better understand the potential mechanisms of hyperbaric oxygen (HBO) treatment alleviating spinal cord injury (SCI). Materials and methods: The SCI model was firstly built in mice, which were randomly divided into three groups: Sham (SH), SCI and HBO groups, followed by hind limb motor function evaluation. Then the spinal cord tissue samples were harvested for histological evaluation and genome-wide transcriptional analysis at 1 week after injury. Finally, some oxidative stress and cell death related differently expressed genes were selected to be analyzed followed by the functional analysis. Results: HBO treatment significantly improved the recovery of hind limb motor function and decreased the histology score compared to the SCI group. In the genome-wide transcriptional analysis, a total of 76 common differently expressed gene among the three groups were obtained at 1 week after injury, which were enriched in functional pathway such as ferroptosis, calcium signaling pathway, serotonergic synapse, etc. Trends in expression of the six genes were consistent with transcriptional analysis. Conclusions: Identified differentially expressed genes and related signaling pathways may be associated with HBO treatment alleviating second spinal cord injury. These results contribute to elucidate the mechanism of HBO in the treatment of SCI.
2021-10-08 | GSE185301 | GEO
Project description:PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice. 29 microarrays including hybridizations of control FVB/N PFC, control FVB/N CPu,control S transgenics PFC, control S transgenics CPu, control R transgenics PFC, control R transgenice CPu, MPTP FVB/N PFC, MPTP FVB/N CPu, MPTP S transgenics PFC, MPTP S transgenics CPu, MPTP R transgenics PFC and MPTP R transgenice CPu mRNA.
2012-01-09 | E-GEOD-31458 | biostudies-arrayexpress
Project description:Obesity during menopause contributes risk for mood disorders, dementia and Alzheimer’s disease (AD). Given the high prevalence of obesity among postmenopausal women there is an urgent need to evaluate the efficacy of hormone therapy (HT) administered immediately (vs delayed) at menopause in different brain regions involved in memory and cognition. Here, and to more closely replicate the endocrine environment of obese postmenopausal women, either on or off HT, middle-aged female rhesus macaques were ovariectomized/hysterectomized (OvH) and maintained on a high-fat, high-sugar, obesogenic Western-style diet (WSD) for 30 months; half of the animals received HT immediately after OvH and half served as placebo controls. RNAseq of the occipital (OC) and prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMG), identified 293, 379, 505 and 4,993 differentially expressed genes (DEGs), respectively. Pathway enrichment analysis, identified an activation of neuroinflammation in OC and HIP, but an inhibition in the AMG with HT. Synaptogenesis, circadian rhythm, mitochondrial dysfunction, mTOR, glutamate, serotonin, GABA, dopamine, noradrenaline/adrenaline, glucocorticoid receptor signaling. neuronal NOS and amyloid processing were exclusively enriched in AMG. As compared to the placebo control group, most of these signaling pathways are downregulated after HT, suggesting a protective effect of HT in OvH females under a WSD. Overall, our results suggest that a chronic obesogenic diet may induce a wide range of alterations in multiple signaling pathways that are linked to age-associated brain pathology and dementia. In these individuals, HT seems to have a protective effect against neuroinflammation, amyloid beta depositions and tau tangles formation.
2021-05-11 | GSE174153 | GEO
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
2016-07-27 | E-GEOD-81672 | biostudies-arrayexpress
Project description:snRNA-seq on hippocampus (Hip) and prefrontal lobe cortex (PFC) tissue in mice
| PRJNA837074 | ENA
Project description:To identify gene expression changes associated with Crtc1 deficiency, we performed genome-wide transcriptome profile analyses by using mouse cDNA microarrays in the cortex of Crtc1‒/‒ and WT female mice BACKGROUND: Recent studies involve the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brain of mood disorders patients. We showed that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate neurobehavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. METHODS: The molecular basis of the behavioral phenotype of Crtc1‒/‒ mice was further examined using microarray analysis. We characterized Agmat expression in the prefrontal cortex (PFC) and hippocampus (HIP) by quantitative polymerase chain reaction (qPCR), Western blot (WB) analysis, and confocal immunofluorescence microscopy. The antidepressant effect of agmatine was assessed by the forced swim test (FST). Brain-derived neurotrophic factor (BDNF) levels and eukaryotic elongation factor 2 (eEF2) phosphorylation were measured by WB. RESULTS: Microarray, qPCR and WB analyses revealed an upregulation of Agmat in Crtc1‒/‒ PFC and HIP, where immunofluorescence microscopy showed more Agmat-expressing cells, notably parvalbumin- and somatostatin-interneurons. Acute agmatine treatment efficiently improved depressive-like behavior of Crtc1‒/‒ mice in the FST, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit induced by upregulated Agmat. In WT mice, agmatine rapidly increased BDNF levels and eEF2 dephosphorylation, indicating that it might be a fast–acting antidepressant with NMDA receptor antagonist properties. CONCLUSIONS: Collectively, these findings support the involvement of the agmatinergic system in the depressive-like phenotype of Crtc1‒/‒ mice, and allow a better understanding of the agmatinergic system and its putative role in major depression.
2016-07-18 | GSE80633 | GEO
Project description:We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities. Keywords: Age series Human, chimpanzee and rhesus macaque post-mortem brain samples from the superior frontal gyrus region of the prefrontal cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to Affymetrix® Human Gene 1.0 ST arrays. PFC samples.
2011-12-09 | E-GEOD-22521 | biostudies-arrayexpress