Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA322539 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3575000.fastq.gz | Fastqsanger.gz | |||
| SRR3575010.fastq.gz | Fastqsanger.gz | |||
| SRR3575020.fastq.gz | Fastqsanger.gz | |||
| SRR3575001.fastq.gz | Fastqsanger.gz | |||
| SRR3575011.fastq.gz | Fastqsanger.gz |
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Project description:Neurons in the arcuate nucleus (ARC) sense the fed/fasted state and regulate hunger. ARCAgRP neurons release GABA, NPY and the melanocortin-4 receptor (MC4R) antagonist, AgRP, and are activated by fasting1-4. When stimulated, they rapidly and potently drive hunger5,6. ARCPOMC neurons, in contrast, release the MC4R agonist, α-MSH, and are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and their activity leads to decreased hunger2,4,7. Together, ARCAgRP and ARCPOMC neurons constitute the ARC feeding center. Against this, however, is the finding that ARCPOMC neurons, unlike ARCAgRP neurons, fail to affect food intake over the timescale of minutes to hours following opto- or chemogenetic stimulation5,8. This suggests a rapidly acting component of the ARC satiety pathway is missing. Here, we show that excitatory ARC neurons identified by expression of vesicular glutamate transporter 2 (VGLUT2) and the oxytocin receptor, unlike ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on MC4R-expressing neurons in the paraventricular hypothalamus (PVHMC4R neurons), which are known to mediate satiety9. ARCPOMC neurons also send dense projections to the PVH. Importantly, the α-MSH they release post-synaptically potentiates glutamatergic synaptic activity onto PVHMC4R neurons – including that emanating from ARCVglut2 neurons. This suggests a means by which α-MSH can bring about satiety – via postsynaptic potentiation of this novel ARCVglut2 to PVHMC4R satiety circuit. Thus, while fast (GABA and NPY) and slow (AgRP) ARC hunger signals are delivered together by ARCAgRP neurons10,11, the temporally analogous satiety signals from the ARC, glutamate and α-MSH, are delivered separately by two parallel, interacting projections (from ARCVGLUT2 and ARCPOMC neurons). Discovery of this rapidly acting excitatory ARC → PVH satiety circuit, and its regulation by α-MSH, provides new insight into regulation of hunger/satiety.
2016-11-21 | GSE81789 | GEO
Project description:Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVH(MC4R) neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVH(MC4R)→lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVH(MC4R)→LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development.
2016-12-03 | GSE90809 | GEO
Project description:The paraventricular hypothalamus (PVH) controls many behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for functionally-specific PVH neuron projections remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to identify unique neuronal subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to validate and map them spatially. Our spatial transcriptomic atlas resolved 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas, revealing multiple subtypes not described previously and distinct transcriptional programs between neuroendocrine and centrally-projecting neurons. Additionally, projection-based profiling determined neuronal subtypes that project to the parabrachial region (PB) and spinal cord, helping to identify PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, PB-projecting PVH neurons expressing bombesin-like receptor 3 (Brs3) induce satiety, and their silencing causes obesity. Together, this atlas fills a critical gap by contributing high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.
2025-12-16 | GSE303185 | GEO
Project description:The paraventricular hypothalamus (PVH) controls many behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for functionally-specific PVH neuron projections remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to identify unique neuronal subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to validate and map them spatially. Our spatial transcriptomic atlas resolved 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas, revealing multiple subtypes not described previously and distinct transcriptional programs between neuroendocrine and centrally-projecting neurons. Additionally, projection-based profiling determined neuronal subtypes that project to the parabrachial region (PB) and spinal cord, helping to identify PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, PB-projecting PVH neurons expressing bombesin-like receptor 3 (Brs3) induce satiety, and their silencing causes obesity. Together, this atlas fills a critical gap by contributing high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.
2025-12-16 | GSE303083 | GEO
Project description:The paraventricular hypothalamus (PVH) controls many behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for functionally-specific PVH neuron projections remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to identify unique neuronal subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to validate and map them spatially. Our spatial transcriptomic atlas resolved 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas, revealing multiple subtypes not described previously and distinct transcriptional programs between neuroendocrine and centrally-projecting neurons. Additionally, projection-based profiling determined neuronal subtypes that project to the parabrachial region (PB) and spinal cord, helping to identify PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, PB-projecting PVH neurons expressing bombesin-like receptor 3 (Brs3) induce satiety, and their silencing causes obesity. Together, this atlas fills a critical gap by contributing high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.
2025-12-16 | GSE303082 | GEO
Project description:The paraventricular hypothalamus (PVH) controls many behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for functionally-specific PVH neuron projections remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to identify unique neuronal subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to validate and map them spatially. Our spatial transcriptomic atlas resolved 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas, revealing multiple subtypes not described previously and distinct transcriptional programs between neuroendocrine and centrally-projecting neurons. Additionally, projection-based profiling determined neuronal subtypes that project to the parabrachial region (PB) and spinal cord, helping to identify PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, PB-projecting PVH neurons expressing bombesin-like receptor 3 (Brs3) induce satiety, and their silencing causes obesity. Together, this atlas fills a critical gap by contributing high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.
2025-12-16 | GSE303081 | GEO
Project description:The paraventricular hypothalamus (PVH) controls many behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for functionally-specific PVH neuron projections remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to identify unique neuronal subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to validate and map them spatially. Our spatial transcriptomic atlas resolved 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas, revealing multiple subtypes not described previously and distinct transcriptional programs between neuroendocrine and centrally-projecting neurons. Additionally, projection-based profiling determined neuronal subtypes that project to the parabrachial region (PB) and spinal cord, helping to identify PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, PB-projecting PVH neurons expressing bombesin-like receptor 3 (Brs3) induce satiety, and their silencing causes obesity. Together, this atlas fills a critical gap by contributing high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.
2025-12-16 | GSE303080 | GEO
Project description:The paraventricular hypothalamus (PVH) is crucial for food intake control, yet the presynaptic mechanisms underlying PVH neurons remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 results in hyperphagic obesity in mice. RUVBL2-expressing neurons in the PVH (PVHRUVBL2) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVHRUVBL2 neurons form the synaptic connections with POMC and AgRP neurons in the ARC. PVH RUVBL2 KO impairs the excitatory synaptic transmission by reducing presynaptic boutons and synaptic vesicles near active zone. Finally, RUVBL2 overexpression in the PVH suppresses food intake and protects against diet induced obesity. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulation of synaptic plasticity could be an effective way to curb appetite and obesity.
2024-10-02 | GSE249791 | GEO
Project description:Synaptic plasticity has been shown to participate in control of energy homeostasis.The paraventricular hypothalamus (PVH) is crucial for satiety control, though the underlying synaptic mechanisms remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 leads to hyperphagic obesity. We further show that KO of PVH RUVBL2 impairs the excitatory synaptic transmission by reducing presynaptic boutons and altering synaptic vesicle distribution. Chromatin immunoprecipitation-sequencing (ChlP-seq) data show that RUVBL2 binds to the promoters of numerous genes related to synaptic plasticity, in particular synaptic vesicle and neuron axonogenesis. Meanwhile, RNA-seq data show significant changes in the expression of some genes in these two pathways. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulating synaptic plasticity could be an effective way to curb appetite and obesity.
2024-10-02 | GSE252308 | GEO
Project description:The purpose of this study was to identify miRNA that are differentially regulated in the arcuate nucleus of the hypothaamus (ARC) and paraventricular nucleus of the hypothalamus (PVH) after perinatal exposure to maternal obesity.
2024-03-13 | GSE261455 | GEO