Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA168457 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders. Hypocretin (orexin) containing neurons of the lateral hypothalamus are clearly essential for the normal regulation of sleep and wake behaviors, and have been implicated in feeding, anxiety, depression and reward. However, little is known about the molecular phenotypes of these cells, or the mechanism of their specification. We have generated a Hcrt bacTRAP line for comprehensive translational profiling of these neurons in vivo. From this profile, we have identified 188 transcripts, as enriched in these neurons, in additions to thousands more moderately enriched or nominally expressed. We validated many of these at the RNA and protein level, including the transcription factor Lhx9. Lhx9 protein is found in a subset of these neurons, and ablation of these gene results in a 30% loss of Hcrt neuron number, and a profound hypersomnolence in mice. This data suggests that Lhx9 may be important for specification of some Hcrt neurons, and the subsets of these neurons may contribute to discrete sleep phenotypes.
2013-03-22 | GSE38668 | GEO
Project description:The immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders. Hypocretin (orexin) containing neurons of the lateral hypothalamus are clearly essential for the normal regulation of sleep and wake behaviors, and have been implicated in feeding, anxiety, depression and reward. However, little is known about the molecular phenotypes of these cells, or the mechanism of their specification. We have generated a Hcrt bacTRAP line for comprehensive translational profiling of these neurons in vivo. From this profile, we have identified 188 transcripts, as enriched in these neurons, in additions to thousands more moderately enriched or nominally expressed. We validated many of these at the RNA and protein level, including the transcription factor Lhx9. Lhx9 protein is found in a subset of these neurons, and ablation of these gene results in a 30% loss of Hcrt neuron number, and a profound hypersomnolence in mice. This data suggests that Lhx9 may be important for specification of some Hcrt neurons, and the subsets of these neurons may contribute to discrete sleep phenotypes. Four independent TRAP replicates were collected, and total RNA from both the immunoprecipitate(IP) and unbound(total) fractions were seperately amplified and hybridized. Unbound fractions are provided to serve as total RNA controls for the tissue. Biological replicates are GCRMA normalized within groups. Following averaging of replicates, we recommend further global normalization between groups, using affymetrix biotinylated controls, to correct for any broad biases in scanning and hybridization. Finally for many analyses, we also recommend filtering to remove those probesets with low IP/Total fold change values from each cell type(see PMID:20962086). Researchers can contact us for spreadsheets where these additional steps have been completed.
2013-03-22 | E-GEOD-38668 | biostudies-arrayexpress
Project description:Oncogenic KRAS signaling is required for tumor survival in cancers that harbor KRAS mutations. We recently performed a genome-scale expression screen to identify genes that bypass KRAS dependency. Here we demonstrate that the developmental transcription factor LHX9 rescues KRAS suppression in vitro and xenograft models. Furthermore, LHX9 decreases cell sensitivity to KRASG12C and MEK1/2 inhibitors. LHX9 promotes transcriptional changes associated with KRAS. Importantly, YAP1 upregulation by LHX9 is required for the rescue of KRAS suppression. Together we identify LHX9 as a YAP1 transcriptional regulator that permits KRAS-dependent cells to proliferate without KRAS expression.
2018-12-01 | GSE116823 | GEO
Project description:Oncogenic KRAS signaling is required for tumor survival in cancers that harbor KRAS mutations. We recently performed a genome-scale expression screen to identify genes that bypass KRAS dependency. Here we demonstrate that the developmental transcription factor LHX9 rescues KRAS suppression in vitro and xenograft models. Furthermore, LHX9 decreases cell sensitivity to KRASG12C and MEK1/2 inhibitors. LHX9 promotes transcriptional changes associated with KRAS. Importantly, YAP1 upregulation by LHX9 is required for the rescue of KRAS suppression. Together we identify LHX9 as a YAP1 transcriptional regulator that permits KRAS-dependent cells to proliferate without KRAS expression.
2018-12-01 | GSE116822 | GEO
Project description:Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this RNA-Seq study, we discovered that treating cultured DRG neurons with Schwann cell-conditioned media or PGE2 increased the expression of several genes required for neuronal maturation and excitability, including voltage-gated sodium channels.
2024-06-03 | GSE268606 | GEO
Project description:Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this scRNAseq study, we found that inactivating PGE2 synthesis in Schwann cells, in vivo, impaired somatosensory neuron maturation, with the most dramatic effects on nociceptor and proprioceptor somatosensory neuron subtypes.
2024-06-03 | GSE268625 | GEO
Project description:Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this scRNAseq study, we found that inactivating PGE2 synthesis in Schwann cells in vivo impaired somatosensory neuron maturation, with the most dramatic effects on nociceptor and proprioceptor somatosensory neuron subtypes.
2024-06-03 | GSE268620 | GEO
Project description:During nervous system development, pioneer neurons are the first to extend their axons into target tissues, creating a scaffold for follower neurons. Despite years of study, whether pioneer neurons are a molecularly distinct population is unknown. Analysis of zebrafish posterior lateral line (pLL) sensory neurons during axon growth using single-cell RNA sequencing (scRNA-seq) revealed that pioneer and follower neurons are transcriptionally distinct. Expression profiling of differentiating pLL progenitors defined follower as the ground state, whereas “pioneer” is a later developmental state. The scRNA-seq data revealed active retinoic acid (RA) signaling in followers, but not in pioneers. Modulation of RA signaling within single pLL neurons showed that its downregulation in pioneers is necessary for expression of neurotrophic factor receptor ret, which is required for correct targeting of pioneer axons. Our study provided insights into the molecular landscape of pioneer neurons and revealed the regulatory role of RA signaling in their development.
2024-06-01 | GSE264323 | GEO
Project description:During nervous system development, pioneer neurons are the first to extend their axons into target tissues, creating a scaffold for follower neurons. Despite years of study, whether pioneer neurons are a molecularly distinct population is unknown. Analysis of zebrafish posterior lateral line (pLL) sensory neurons during axon growth using single-cell RNA sequencing (scRNA-seq) revealed that pioneer and follower neurons are transcriptionally distinct. Expression profiling of differentiating pLL progenitors defined follower as the ground state, whereas “pioneer” is a later developmental state. The scRNA-seq data revealed active retinoic acid (RA) signaling in followers, but not in pioneers. Modulation of RA signaling within single pLL neurons showed that its downregulation in pioneers is necessary for expression of neurotrophic factor receptor ret, which is required for correct targeting of pioneer axons. Our study provided insights into the molecular landscape of pioneer neurons and revealed the regulatory role of RA signaling in their development.
2024-06-01 | GSE266312 | GEO
Project description:Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS
| PRJNA301347 | ENA