Bacterial Information transfer circuit for mammalian gut
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ABSTRACT:
PROVIDER: PRJEB28380 | ENA |
REPOSITORIES: ENA
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Project description:The mouse visual system serves as an accessible model to understand mammalian circuit wiring. Despite rich knowledge in retinal circuits, the long-range connectivity map from distinct retinal ganglion cell (RGC) types to diverse brain neuron types remains unknown. Here we developed an integrated approach, named Trans-Seq, to map RGC to superior collicular (SC) circuits. Trans-Seq combines a fluorescent anterograde transsynaptic tracer, consisting of codon-optimized wheat germ agglutinin fused to mCherry, with single-cell RNA Sequencing. We used Trans-Seq to classify SC neuron types innervated by genetically-defined RGC types and predicted a neuronal pair from αRGCs to Nephronectin-positive wide-field neurons (NPWFs). We validated this connection using genetic labeling, electrophysiology, and retrograde tracing. We then utilized transcriptomic data from Trans-Seq to identify Nephronectin as a determinant for selective synaptic choice from αRGC to NPWFs via binding to Integrin-α8β1. The Trans-Seq approach can be broadly applied for postsynaptic circuit discovery from genetically-defined presynaptic neurons.
2022-05-07 | GSE202257 | GEO
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Project description:Neural circuits in the spinal cord have a critical role in integrating sensory information and descending commands to coordinate body movements. Defining the functional diversity of spinal neurons is therefore essential for understanding the mechanisms underlying motor control. In this study, by combining anatomical, molecular, and functional analyses in mice, we identified and characterized a subtype of ascending spinal neurons belonging to the V0g family. We found that V0g ascending neurons are integrated in lumbar sensorimotor circuits and their function is specifically required for the execution of precise limb movements necessary for skilled locomotion. This work advances our understanding of the functional organization of V0 neurons and highlights a previously unappreciated role in adjusting body movements to the more demanding needs of skilled locomotor tasks
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Project description:Gene syntax---the order and arrangement of genes and their regulatory elements---shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus profoundly impacts the transcription of nearby adjacent genes, but the molecular basis of this effect remains poorly understood. Here, using integrated reporter circuits in human cells, we show that the reciprocal effects of transcription and DNA supercoiling, which we term supercoiling-mediated feedback, regulates expression of adjacent genes in a syntax-specific manner. Using a suite of chromatin state assays, we measure syntax- and induction-dependent formation of chromatin structures in human induced pluripotent stem cells. Applying syntax as a design parameter and without altering sequence or copy number, we built compact gene circuits, tuning the expression mean, noise, and stoichiometry across diverse delivery methods and cell types. Integrating supercoiling-mediated feedback into models of gene regulation will expand our understanding of native systems and enhance the design of synthetic gene circuits.
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Project description:Gene syntax---the order and arrangement of genes and their regulatory elements---shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus profoundly impacts the transcription of nearby adjacent genes, but the molecular basis of this effect remains poorly understood. Here, using integrated reporter circuits in human cells, we show that the reciprocal effects of transcription and DNA supercoiling, which we term supercoiling-mediated feedback, regulates expression of adjacent genes in a syntax-specific manner. Using a suite of chromatin state assays, we measure syntax- and induction-dependent formation of chromatin structures in human induced pluripotent stem cells. Applying syntax as a design parameter and without altering sequence or copy number, we built compact gene circuits, tuning the expression mean, noise, and stoichiometry across diverse delivery methods and cell types. Integrating supercoiling-mediated feedback into models of gene regulation will expand our understanding of native systems and enhance the design of synthetic gene circuits.
2026-03-02 | GSE316694 | GEO
Project description:Gene syntax---the order and arrangement of genes and their regulatory elements---shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus profoundly impacts the transcription of nearby adjacent genes, but the molecular basis of this effect remains poorly understood. Here, using integrated reporter circuits in human cells, we show that the reciprocal effects of transcription and DNA supercoiling, which we term supercoiling-mediated feedback, regulates expression of adjacent genes in a syntax-specific manner. Using a suite of chromatin state assays, we measure syntax- and induction-dependent formation of chromatin structures in human induced pluripotent stem cells. Applying syntax as a design parameter and without altering sequence or copy number, we built compact gene circuits, tuning the expression mean, noise, and stoichiometry across diverse delivery methods and cell types. Integrating supercoiling-mediated feedback into models of gene regulation will expand our understanding of native systems and enhance the design of synthetic gene circuits.
2026-03-02 | GSE316693 | GEO
Project description:Gene syntax---the order and arrangement of genes and their regulatory elements---shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus profoundly impacts the transcription of nearby adjacent genes, but the molecular basis of this effect remains poorly understood. Here, using integrated reporter circuits in human cells, we show that the reciprocal effects of transcription and DNA supercoiling, which we term supercoiling-mediated feedback, regulates expression of adjacent genes in a syntax-specific manner. Using a suite of chromatin state assays, we measure syntax- and induction-dependent formation of chromatin structures in human induced pluripotent stem cells. Applying syntax as a design parameter and without altering sequence or copy number, we built compact gene circuits, tuning the expression mean, noise, and stoichiometry across diverse delivery methods and cell types. Integrating supercoiling-mediated feedback into models of gene regulation will expand our understanding of native systems and enhance the design of synthetic gene circuits.
2026-03-02 | GSE316692 | GEO
Project description:Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit, yet the design features of cell circuits involved in tissue homeostasis are unknown. Here we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. We employed analytical screening of all possible two-cell circuit topologies and defined the circuit features sufficient for stability, including environmental constraint and negative feedback regulation. Moreover, we discovered that cell-cell contact was essential for the stability of the macrophage-fibroblast circuit. These findings highlight general principles of cell circuit design, and provide a new perspective on quantitative understanding of tissue homeostasis.
2018-02-08 | GSE104511 | GEO
Project description:Mechanobiologic signals play critical roles in regulating cellular responses under both physiologic and pathologic conditions. Using a combination of synthetic biology and tissue engineering, we developed a mechanically-responsive bioartificial tissue that responds to mechanical loading to produce a pre-programmed therapeutic biologic drug. By deconstructing the signaling networks induced by activation the mechanically-sensitive ion channel transient receptor potential vanilloid 4 (TRPV4), we synthesized synthetic TRPV4-responsive genetic circuits in chondrocytes. These cells were then engineered into living tissues that respond to mechanical compression to drive the production of the anti-inflammatory drug interleukin-1 receptor antagonist. Mechanical loading of these tissues in the presence of the cytokine interleukin-1 protected constructs from inflammatory degradation. This “mechanogenetic” approach enables long-term autonomous delivery of therapeutic compounds that is driven by physiologically-relevant mechanical loading with cell-scale mechanical force resolution. The development of synthetic mechanogenetic gene circuits provides a novel approach for the autonomous regulation of cell-based drug delivery systems.
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Project description:In mammalian systems, extracellular small RNAs can operate in a paracrine manner to communicate information between cells, relying on transport within vesicles. “Foreign” small RNAs derived from bacteria, plants and parasites have also been detected in mammalian body fluids, sparking interest in whether these could mediate inter-species communication. However, there is no mechanistic framework for RNA-mediated interspecies communication and the active movement of RNA via vesicles has not been shown outside of mammals. Here we demonstrate that specific microRNAs and Y RNAs are packaged into vesicles secreted by a gastrointestinal nematode, Heligmosomoides polygyrus, which naturally infects mice. Total RNA was extracted from the serum of mice infected with Litomosoides sigmodontis at 60 days post infection
2014-11-26 | E-GEOD-60021 | biostudies-arrayexpress