Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1034128 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26620787.fastq.gz | Fastqsanger.gz | |||
| SRR26620788.fastq.gz | Fastqsanger.gz | |||
| SRR26620789.fastq.gz | Fastqsanger.gz | |||
| SRR26620790.fastq.gz | Fastqsanger.gz | |||
| SRR26620791.fastq.gz | Fastqsanger.gz |
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Project description:Notch signaling is an evolutionarily conserved pathway for specifying binary neuronal fates, yet how it specifies different fates in different contexts remains elusive. In our accompanying paper, using the Drosophila lamina neuron types (L1-L5) as a model, we show that the primary homeodomain transcription factor (HDTF) Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates. Here we test the hypothesis that Notch signaling enables Bsh to differentially specify L4 and L5 fates. We show asymmetric Notch signaling between newborn L4 and L5 neurons, but they are not siblings; rather, Notch signaling in L4 is due to Delta expression in adjacent L1 neurons. While Notch signaling and Bsh expression are mutually independent, Notch is necessary and sufficient for Bsh to specify L4 fate over L5. The NotchON L4, compared to NotchOFF L5, has a distinct open chromatin landscape which allows Bsh to bind distinct genomic loci, leading to L4-specific identity gene transcription. We propose a novel model in which Notch signaling is integrated with the primary HDTF activity to diversify neuron types by directly or indirectly generating a distinct open chromatin landscape that constrains the pool of genes that a primary HDTF can activate.
2023-11-12 | GSE247239 | GEO
Project description:How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina neuron types (L1-L5), we show that the primary homeodomain transcription factor (HDTF) Brain-specific homeobox (Bsh) is initiated in progenitors and maintained in L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates while repressing the HDTF Zfh1 to prevent ectopic L1/L3 fates (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating lamina neuronal diversity for normal visual sensitivity. Subsequently, in L4 neurons, Bsh and Ap function in a feed-forward loop to activate the synapse recognition molecule DIP-β, thereby bridging neuronal fate decision to synaptic connectivity. Expression of a Bsh:Dam specifically in L4 reveals Bsh binding to the DIP-β locus and additional candidate L4 functional identity genes. We propose that HDTFs function hierarchically to coordinate neuronal molecular identity, circuit formation, and function. Hierarchical HDTFs may represent a conserved mechanism for linking neuronal diversity to circuit assembly and function.
2023-11-05 | GSE246726 | GEO
Project description:Summary
Extracellular vesicles (EVs) facilitate intercellular communication by transferring cargo between cells in a variety of tissues. However, how EVs achieve cell type-specific intercellular communication is still largely unknown. We found that Notch1 and Notch2 proteins are expressed on the surface of neuronal EVs that have been generated in response to neuronal excitatory synaptic activity. Notch ligands bind these EVs on the neuronal plasma membrane, trigger their internalization, activate the Notch signaling pathway, and drive the expression of Notch target genes. The generation of these neuronal EVs requires the ESCRT-associated protein Alix. Adult Alix conditional knockout mice have reduced hippocampal Notch signaling activation and glutamatergic synaptic protein expression. Thus, EVs facilitate neuron to neuron communication via the Notch receptor-ligand system in the brain.
2023-12-06 | MSV000093592 | MassIVE
Project description:The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.
2024-02-19 | GSE231774 | GEO
Project description:A large fraction of the mammalian genome is organized into inactive chromosomal domains associated with the nuclear lamina. Using genomic repositioning assays we show that Lamina associated domains (LADs), spanning the developmentally regulated IgH and Cyp3a loci, contain transportable DNA regions that associate chromatin with the nuclear lamina and repress gene activity in fibroblasts. We characterized DNA regions within LADs that are functionally capable of positioning chromatin domains at the inner nuclear membrane (INM) lamina. We mapped and characterized the IgH and other LADs in murine fibroblasts. We show that these murine LADs have a unique chromatin structure with discrete boundaries. We demonstrate DNA regions within LADs that are capable of directing the association of chromatin domains with the INM-lamina as well as the silencing of a co-integrated reporter gene.
2012-02-24 | E-GEOD-36048 | biostudies-arrayexpress
Project description:The ability of cells to stably maintain their fate is governed by specific transcription regulators. Here, we show that the Scalloped (Sd) and Nervous fingers-1 (Nerfin-1) transcription factors physically and functionally interact to maintain medulla neuron fate in the Drosophila melanogaster CNS. Using Targeted DamID we find that Sd and Nerfin-1 occupy a highly overlapping set of target genes, including regulators of neural stem cell and neuron fate, and signalling pathways that regulate CNS development such as Notch and Hippo. Modulation of either Sd or Nerfin-1 activity causes medulla neurons to dedifferentiate to a stem cell-like state and this is mediated at least in part by Notch pathway deregulation. Intriguingly, orthologues of Sd and Nerfin-1 have also been implicated in control of neuronal cell fate decisions in both worms and mammals. Our data indicate that this transcription factor pair exhibits remarkable biochemical and functional conservation across metazoans.
2018-10-03 | GSE120731 | GEO
Project description:The mammalian telencephalon contains a tremendous diversity of GABAergic projection neuron and interneuron types, that originate in a germinal zone of the embryonic basal ganglia. How genetic information in this transient structure is transformed into different cell types is not yet fully understood. Using a combination of in vivo lineage tracing, CRISPR perturbation and ChIP-seq in mice, we found that the transcription factor MEIS2 favors the development of projection neurons through genomic binding sites in regulatory enhancers of projection neuron specific genes. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity towards these sites. In interneurons, the activation of projection neuron specific enhancers by MEIS2 and DLX5 is repressed by the transcription factor LHX6. When MEIS2 carries a mutation associated with intellectual disability in humans, it is less effective at activating enhancers involved in projection neuron development. This suggests that GABAergic differentiation may be impaired in patients carrying this mutation. Our research has uncovered a mechanism by which the selective activation of enhancers plays a crucial role in the establishment of neuronal identity, as well as in potential pathological mechanisms
2024-02-19 | GSE231777 | GEO
Project description:Bacteroides, that expresses bile salt hydrolase (BSH), is considered as a potential drug target for metabolic diseases. In the present study, BSH-expressing Bacteroides was found to be enriched in two different CRC mouse models and colonization of nonenterotoxigenic Bacteroides species, such as B. fragilis 9343 or B. vulgatus , enhanced CRC growth. Expression of the 9343 bsh gene in B. fragilis 638R, a bsh - lacking strain, enabled more bile acids to escape into the colon and accelerated CRC progression . The presence of BSH activated WNT signaling and upregulated CCL28 expression dependent on b-catenin in colon tumors. The activated b-catenin/CCL28 axis elevated intra-tumororal immunosuppressive CD25+ FOXP3+ T reg cells. Anti-CCL28 antibody reversed microbial BSH amplificationinduced immunosuppression. Inhibition of BSH reduced CRC progression, coincident with suppression of WNT signaling and CCL28 expression. These findings provide a novel insight into the pro-carcinogenetic role of NTBF in CRC and characterize BSH as a potential target for CRC treatment.
2022-12-17 | GSE190298 | GEO
Project description:Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the conserved microbial functions that influence host energy metabolism and adiposity have not been determined. Here we show that bacterial bile salt hydrolase (BSH) controls a microbe-host dialogue which functionally regulates host lipid metabolism and weight gain. Expression of cloned BSH enzymes in the GI tract of gnotobiotic or conventional mice significantly altered plasma bile acid signatures and regulated transcription of key genes involved in lipid metabolism (PPARgamma angptl4), cholesterol metabolism (abcg5/8), gastrointestinal homeostasis (regIIIgamma) and circadian rhythm (dbp, per1/2) in the liver or small intestine. High-level expression of BSH in conventionally raised mice resulted in significant reduction of host weight-gain, plasma cholesterol and liver triglycerides. We demonstrate that bacterial BSH activity significantly impacts systemic metabolic processes and adiposity in the host, and represents a key mechanistic target for the control of obesity and hypercholesterolaemia.
2014-05-09 | GSE46952 | GEO
Project description:We performed single-cell RNA-seq (10x Chromium 3' v.2) on dissociated single cell suspensions from mouse (C57BL/6) osmosensory brain nuclei - subfornical organ (SFO) and organum vasculosum lamina terminalis (OVLT) to determine transcriptomic cell types in each structure. We identified 12 and 13 major cell classes as well as 8 neuron types in each for SFO and OVLT respectively. Furthermore, we studied how different types of thirst signals (osmotic thirst, hypovolemic thirst, chronic water deprivation) engage this cellular diversity by performing single cell RNA-seq based (10x Chromium 3' v.3.0) stimulus to cell-type mapping, where dissociation related transcriptional artifacts were suppressed through a modified tissue preparation protocol involving a transcriptional blocker and dissociation at room temperature. This approach revealed the endogenous immediate early gene expression triggered by distinct thirst stimuli in SFO and OVLT cells. By analyzing immediate early gene expression that is driven by changes in neural activity (Fos) we identified excitatory neuron types in SFO and OVLT that are uniquely tuned to distinct thirst states.
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