Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338177 | ENA |
REPOSITORIES: ENA
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Project description:Olfaction is fundamental for survival but there is little known about the connection between smell perception and metabolism. In this study we implemented IGF1R knockout mice in the olfactory sensory neurons, by olfactory marker protetin (OMP) Cre specific recombination, and investigated metabolic parameters, smell perception and transcriptome sequencing. We could demonstrate that IGF1R knockout in the olfactory sensory neurons results in enhanced smell perception, insulin resistance under normal chow diet conditions and increased adiposity in mice fed control diet. Transcriptome analysis of the olfactory epithelium revealed differential expression of markers for mature and immature olfactory sensory neurons, being down-regulated and up- regulated respectively, pointing to differentiation-dependent changes that result in increased olfactory perception. Collectively, this study provides evidence that enhanced smell perception can result in insulin resistance and increased adiposity.
2017-05-22 | GSE85329 | GEO
Project description:Lamins, the major components of the nuclear lamina, have diverse functions in many cellular processes. Despite broad expression, lamins have been implicated in cell type-specific roles in development, aging and disease by regulating gene expression. Yet, due to the lack of in depth lineage-specific functional studies, it remains unclear whether or how lamins regulate cell type-specific functions. Using targeted knockout of lamin B1 in the olfactory sensory neuron lineage, we show that lamin B1 is not required for early stages of olfactory sensory neuron differentiation but is needed for formation of mature neurons that properly respond to odor stimulation. Lamin B1 mutant cells exhibited decreased expression of genes involved in mature neuron function, increased expression of genes atypical of the olfactory lineage and clustered nuclear pore distribution. These results demonstrate that the universally expressed lamin B1 regulates cell type-specific gene expression and terminal differentiation.
2017-05-01 | GSE80290 | GEO
Project description:Lamins, the major components of the nuclear lamina, have diverse functions in many cellular processes. Despite broad expression, lamins have been implicated in cell type-specific roles in development, aging and disease by regulating gene expression. Yet, due to the lack of in depth lineage-specific functional studies, it remains unclear whether or how lamins regulate cell type-specific functions. Using targeted knockout of lamin B1 in the olfactory sensory neuron lineage, we show that lamin B1 is not required for early stages of olfactory sensory neuron differentiation but is needed for formation of mature neurons that properly respond to odor stimulation. Lamin B1 mutant cells exhibited decreased expression of genes involved in mature neuron function, increased expression of genes atypical of the olfactory lineage and clustered nuclear pore distribution. These results demonstrate that the universally expressed lamin B1 regulates cell type-specific gene expression and terminal differentiation.
2017-05-01 | GSE80044 | GEO
Project description:Emx2 is a homeobox transcription factor that plays a critical role in development. Olfactory sensory neuron axons from Emx2 knockout mice fail to innervate their target tissue, the olfactory bulb. Homeobox transcription factors may also play an important role in olfactory receptor expression. We used microarrays to analyze differences in mRNA abundance in the olfactory epithelium of Emx2 wildtype and knockout embryonic day 18.5 mice. Keywords: Knockout-Wildtype comparision
2008-10-15 | GSE12135 | GEO
Project description:Emx2 is a homeobox transcription factor that plays a critical role in development. Olfactory sensory neuron axons from Emx2 knockout mice fail to innervate their target tissue, the olfactory bulb. Homeobox transcription factors may also play an important role in olfactory receptor expression. We used microarrays to analyze differences in mRNA abundance in the olfactory epithelium of Emx2 wildtype and knockout embryonic day 18.5 mice. Keywords: Knockout-Wildtype comparision Total RNA from 9 Emx2 wildtype and 9 Emx2 knockout mice was analyzed. Equal amounts of RNA from 3 animals was pooled to create one biological sample, 3 pools per genotype, 6 chips total. RNA was hybridized to the Affymetrix Mouse Exon 1.0 ST array.
2008-10-15 | E-GEOD-12135 | biostudies-arrayexpress
Project description:In this study, we aimed at uncovering the molecular mechanisms underlying POMC neuron sensory activation and the mediated behavioral and metabolic processes. Unexpectedly, we found that glycogen metabolism is rapidly engaged in POMC neurons upon sensory food perception. Genetic deletion of glycogen synthase, the sole enzyme able to make glycogen in vivo, in POMC neurons impedes food-related sensory activation while causing impairments in food awareness, short-term food intake and insulin release. These perturbations associate with whole-body metabolic defects, including overweight and insulin resistance, that are exacerbated by high-dense diets or ageing. Collectively, our study identifies glycogen metabolism as an unanticipated mechanistic driver of POMC neuron sensory activation and provides paradigm-shift evidences of the importance of neuronal glycogen for physiology.
2024-01-31 | GSE224274 | GEO
Project description:Decreased skeletal muscle strength and mitochondrial dysfunction are characteristic of diabetes. Action of insulin through insulin receptor (IR) and IGF-1 receptor (IGF1R) maintain muscle mass via suppression of FoxOs, but whether FoxO activation coordinates atrophy in concert with mitochondrial dysfunction is unknown. In the absence of systemic glucose or lipid abnormalities, muscle-specific IR knockout (MIRKO) or combined IR/IGF1R knockout (MIGIRKO) impaired mitochondrial respiration, decreased ATP production, and increased ROS. These mitochondrial abnormalities were not present in muscle-specific IR/IGF1R and FoxO1/3/4 quintuple knockout mice (QKO). Although autophagy was increased when IR/IGF1R were deleted in muscle, mitophagy was not increased. Mechanistically, RNA-seq revealed that complex-I core subunits were decreased in MIGIRKO muscle, and these were reversed with FoxO knockout. Thus, insulin-deficient diabetes or loss of insulin/IGF-1 action in muscle decreases complex-I driven mitochondrial respiration and supercomplex assembly, in part by FoxO-mediated repression of Complex-I subunit expression.
2021-07-21 | GSE178356 | GEO
Project description:Adaptation of liver to the postprandial state requires coordinate regulation of protein synthesis and folding aligned with changes in lipid metabolism. Here we demonstrate that sensory food perception is sufficient to elicit early activation of hepatic mTOR-signaling, Xbp1-splicing, increased expression of ER-stress genes and phosphatidylcholine synthesis, which translate into a rapid morphological ER-remodeling. These responses overlap with those activated during refeeding, where they are maintained and constantly increase upon nutrient supply. Sensory food perception activates POMC-neurons in the hypothalamus, optogenetic activation of POMC-neurons activates hepatic mTOR-signaling and Xbp1-splicing and lack of MC4R-expression attenuates these responses to sensory food perception. Chemogenetic POMC-neuron activation promotes sympathetic nerve activity (SNA) subserving the liver, and norepinephrine evokes the same responses in hepatocytes in vitro and liver in vivo as observed upon sensory food perception. Collectively, our experiments unravel that sensory food perception coordinatly primes postprandrial liver ER adaption through a melanocortin-SNA-mTOR-Xbp1s-axis
2018-10-31 | GSE118973 | GEO
Project description:Recognition of environmental cues is essential for the survival of all organisms. Precise transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory receptor neurons (ORNs), thermosensory and hygrosensory neurons from the third antennal segment at an early developmental and adult stage. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using these receptors and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuronal types across multiple developmental stages. Cell-type-specific transcriptomes, in part, reflected axon trajectory choices in early development and sensory modality in adults. Our analysis also uncovered type specific and broadly expressed genes that could modulate adult sensory responses. Collectively, our data reveal important transcriptomic features of sensory neuron biology and provides a resource for future studies of their development and physiology.
2021-02-01 | GSE162121 | GEO
Project description:Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein M-NM-2M-NM-3 subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron. Total 6 samples were analyzed-3 controls & 3 samples
2013-12-16 | E-GEOD-53334 | biostudies-arrayexpress