High-throughput RNA seq data of mouse embryonic stem cells and intermediate states throughout their differentiation into motor neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE106526 | GEO | 2018/08/31
REPOSITORIES: GEO
Similar Datasets
Project description:Sensory neuron mechanically-activated slowly adapting currents have been linked to noxious mechanosensation. We identified a Conotoxin, Noxious Mechanosensation Blocker -1, that blocks such currents selectively. Using an active biotinylated form of the toxin we identified 67 binding proteins in sensory neurons and sensory neuron-derived cell lines using mass spectrometry. Annexin A6 was the most frequently identified binding protein. Annexin A6 knockout mice showed an enhanced sensitivity to mechanical stimuli. Rapidly adapting currents were enhanced and slowly adapting channels diminished. The percentage of neurons expressing slowly adapting currents fell and non-responsive neurons increased. Conversely, overexpression of annexin A6 in DRG neurons inhibited rapidly adapting currents without effects on slowly adapting currents. Co-expression of annexin A6 with Piezo 2 led to an inhibition of Piezo-mediated rapidly adapting currents. AAV-mediated gene delivery of annexin A6 to sensory neurons in a mouse model of osteoarthritis attenuated mechanical pain. These data demonstrate a role for annexin A6 in somatosensory mechanotransduction.
2018-04-17 | PXD005718 | Pride
Project description:This a model from the article:
Ionic mechanism of electrical alternans.
Fox JJ, McHarg JL, Gilmour RF Jr. Am J Physiol Heart Circ Physiol
2002 Feb;282(2):H516-30 11788399
,
Abstract:
Although alternans of action potential duration (APD) is a robust feature of the
rapidly paced canine ventricle, currently available ionic models of cardiac
myocytes do not recreate this phenomenon. To address this problem, we developed
a new ionic model using formulations of currents based on previous models and
recent experimental data. Compared with existing models, the inward rectifier
K(+) current (I(K1)) was decreased at depolarized potentials, the maximum
conductance and rectification of the rapid component of the delayed rectifier
K(+) current (I(Kr)) were increased, and I(Kr) activation kinetics were slowed.
The slow component of the delayed rectifier K(+) current (I(Ks)) was increased
in magnitude and activation shifted to less positive voltages, and the L-type
Ca(2+) current (I(Ca)) was modified to produce a smaller, more rapidly
inactivating current. Finally, a simplified form of intracellular calcium
dynamics was adopted. In this model, APD alternans occurred at cycle lengths =
150-210 ms, with a maximum alternans amplitude of 39 ms. APD alternans was
suppressed by decreasing I(Ca) magnitude or calcium-induced inactivation and by
increasing the magnitude of I(K1), I(Kr), or I(Ks). These results establish an
ionic basis for APD alternans, which should facilitate the development of
pharmacological approaches to eliminating alternans.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Fox JJ, McHarg JL, Gilmour RF Jr. (2002) - version02
The original CellML model was created by:
Noble, Penny,
penny.noble@dpag.oc.ac.uk
Oxford University
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL0911665321 | BioModels
Project description:Protein kinase A is a downstream effector of many inflammatory mediators that induce pain hypersensitivity by increasing the mechanosensitivity of nociceptive sensory afferent. Here we examine the molecular mechanism underlying protein kinase-Adependent modulation of the mechanically-activated ion channel PIEZO2, which confers mechanosensitivity to many nociceptors. Using phosphorylation site prediction algorithms, we identified multiple putative and highly conserved PKA phosphorylation sites located on intracellular intrinsically disordered regions of PIEZO2. Site-directed mutagenesis and patch-clamp recordings showed that substitution of one or multiple putative PKA sites within a single intracellular domains does not alter PKA-induced PIEZO2 sensitization, whereas mutation of a combination of nine putative sites located on four different intracellular regions completely abolishes PKA-dependent PIEZO2 modulation, suggesting that the effect requires multisite phosphorylation. By demonstrating that PIEZO1 is not modulated by PKA, our data also reveals a previously unrecognized functional difference between PIEZO1 and PIEZO2. Moreover, by demonstrating that PKA only modulates PIEZO2 currents evoked by focal mechanical indentation of the cell, but not currents evoked by pressure-induced membrane stretch, we provide evidence suggesting that PIEZO2 is a polymodal mechanosensor that engages different protein domains for detecting different types of mechanical stimuli.
2023-07-20 | PXD041372 | Pride
Project description:Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor-immunity, is not well-studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We discovered signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells. Moreover, deletion of Piezo1 in myeloid cells protected against cancer and increased survival in poly-microbial sepsis. Mechanistically, we show that mechanical stimulation promotes Piezo1-dependent myeloid cell expansion by suppressing Rb. We further show Piezo1-mediated silencing of Rb is regulated via upregulation of HDAC2. Collectively, our work uncovers Piezo1 as a targetable immune checkpoint that drives immune-suppressive myelopoiesis in cancer and infectious disease.
2020-08-21 | GSE155340 | GEO
Project description:This a model from the article:
Cardiac sodium channel Markov model with temperature dependence and recovery
from inactivation.
Irvine LA, Jafri MS, Winslow RL. Biophys J
1999 Apr;76(4):1868-85 10096885
,
Abstract:
A Markov model of the cardiac sodium channel is presented. The model is similar
to the CA1 hippocampal neuron sodium channel model developed by Kuo and Bean
(1994. Neuron. 12:819-829) with the following modifications: 1) an additional
open state is added; 2) open-inactivated transitions are made voltage-dependent;
and 3) channel rate constants are exponential functions of enthalpy, entropy,
and voltage and have explicit temperature dependence. Model parameters are
determined using a simulated annealing algorithm to minimize the error between
model responses and various experimental data sets. The model reproduces a wide
range of experimental data including ionic currents, gating currents, tail
currents, steady-state inactivation, recovery from inactivation, and open time
distributions over a temperature range of 10 degrees C to 25 degrees C. The
model also predicts measures of single channel activity such as first latency,
probability of a null sweep, and probability of reopening.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Irvine LA, Jafri MS, Winslow RL. (1999) - version02
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@aukland.ac.nz
The University of Auckland
The Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL0848062679 | BioModels
Project description:The mechanisms by which physical forces regulate cells to determine complexities of vascular structure and function are enigmatic. Here we show the role the ion channel subunit Piezo1 (FAM38A). Disruption of mouse Piezo1 gene disturbed vascular development and was embryonic lethal within days of the heart beating to cause blood flow. Importance of Piezo channels as sensors of blood flow was indicated by Piezo1 dependence of shear stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer shear stress sensitivity on cells that otherwise lacked. Downstream of this calcium influx was proteoase activity and spatial organization of endothelial cells to the polarity of the applied force. Without Piezo1, normal endothelial cell organization was lacking. The data suggest Piezo1 channels as pivotal integrators of vascular architacture with physiological mechanical force.
2014-08-08 | PXD001099 | Pride
Project description:To investigate the effect of Piezo1 in the apoptosis of anulus fibrous cells (AFCs) induced by mechanical stretch. We established AFCs in which Piezo1 channel has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of AFCs treated withpLVX-shRNA-Puro(Lv-Ctrl group) and AFCs treated with pLVX-shRNA-Puro-Piezo1(Lv-Piezo1 group).
2022-10-31 | GSE216445 | GEO
Project description:Phenotypic cell-to-cell variability within clonal populations may be amanifestation of "gene expression noise", or it may reflect stablephenotypic variants. Such "non-genetic cell individuality" can arisefrom the slow fluctuations of protein levels in mammalian cells. Thesefluctuations produce persistent cell individuality, thereby rendering aclonal population heterogeneous. However, it remains unknown whetherthis heterogeneity may account for the stochasticity of cell fatedecisions in stem cells which depends on the kinetics that underliesheterogeneity. Here we show that in clonal populations of hematopoieticprogenitor cells, spontaneous "outlier" cells with extremely high or lowexpression levels of the stem cell marker Sca-1 reconstitute theparental distribution of Sca-1 but do so only after more than one week.This slow relaxation is described by a Gaussian-Mixture Model (GMM) thatincorporates noise-driven transitions between discrete subpopulations,suggesting hidden multi-stability within one cell type. Despiteclonality, the Sca-1 outliers had distinct transcriptomes. Although theunique gene expression profiles eventually reversed to that of themedian cells, they lasted long enough to confer a greatly differentproclivity for choosing either the erythroid or myeloid lineages. Preference in lineage choice was associated with elevated expression oflineage-specific transcription factors, such as > 200-fold increase inGATA1 among the erythroid-prone cells, or > 15-fold PU.1 expressionamong myeloid-prone cell. Thus, clonal heterogeneity of gene expressionlevel is not due to independent noise in the expression of individualgenes, but reflects metastable states of a slowly fluctuatingtranscriptome that is distinct in individual cells and may govern thereversible, stochastic priming of multipotent progenitor cells in cellfate decision. Keywords: murine EML cell line In the study presented here, the highest, middle, and lowest 15% Sca-1expressors from a clonal population of EML cells were used to acquireexpression profiles of a total of 46,628 unique genes using the IlluminaMouse-6 v1.1 microbead chips. Here, the Rank-Invariant normalized datais provided along with the individual raw data files.
2008-05-22 | E-GEOD-10772 | biostudies-arrayexpress
Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
2024-02-20 | GSE255882 | GEO
Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
2024-02-20 | GSE255881 | GEO