Spatial Recovery of the Hepatic Lobule Using Single Cell RNA Sequencing
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)
ORGANISM(S): Mus Musculus
SUBMITTER: James Thomson
PROVIDER: GSE116140 | GEO | 2018-07-17
REPOSITORIES: GEO
Dataset's files
primary
| Action | DRS | |||
|---|---|---|---|---|
| GSE116140_Liver_SCnormEC_ALLcells_WavecrestPoly3.csv.gz | Csv |
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This model is described in the article:
Computational Modeling of
Spatiotemporal Ca(2+) Signal Propagation Along Hepatocyte
Cords.
Verma A, Makadia H, Hoek JB,
Ogunnaike BA, Vadigepalli R.
IEEE Trans Biomed Eng 2016 Oct; 63(10):
2047-2055
Abstract:
The purpose of this study is to model the dynamics of
lobular Ca(2+) wave propagation induced by an extracellular
stimulus, and to analyze the effect of spatially systematic
variations in cell-intrinsic signaling parameters on sinusoidal
Ca(2+) response.We developed a computational model of lobular
scale Ca(2+) signaling that accounts for receptor- mediated
initiation of cell-intrinsic Ca(2+) signal in hepatocytes and
its propagation to neighboring hepatocytes through gap
junction-mediated molecular exchange.Analysis of the
simulations showed that a pericentral-to-periportal spatial
gradient in hormone sensitivity and/or rates of IP3 synthesis
underlies the Ca(2+) wave propagation. We simulated specific
cases corresponding to localized disruptions in the graded
pattern of these parameters along a hepatic sinusoid.
Simulations incorporating locally altered parameters exhibited
Ca(2+) waves that do not propagate throughout the hepatic
plate. Increased gap junction coupling restored normal Ca(2+)
wave propagation when hepatocytes with low Ca(2+) signaling
ability were localized in the midlobular or the pericentral
region.Multiple spatial patterns in intracellular signaling
parameters can lead to Ca(2+) wave propagation that is
consistent with the experimentally observed spatial patterns of
Ca(2+) dynamics. Based on simulations and analysis, we predict
that increased gap junction-mediated intercellular coupling can
induce robust Ca(2+) signals in otherwise poorly responsive
hepatocytes, at least partly restoring the sinusoidally
oriented Ca (2+) waves.Our bottom-up model of agonist-evoked
spatial Ca(2+) patterns can be integrated with detailed
descriptions of liver histology to study Ca(2+) regulation at
the tissue level.
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