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Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis
Published on: February 18, 2020
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Distinct cellular states determine calcium signaling response.
Jason Yao1, Anna Pilko1, Roy Wollman2
1Departments of Chemistry and Biochemistry, Integrative Biology and Physiology, and Institute for Quantitative and Computational Biosciences (QCB), UCLA, Los Angeles, CA, USA.
Molecular Systems Biology
|December 17, 2016
Summary
Cellular response variability stems from distinct cell states, not just random fluctuations. Our study identified three such states using calcium signaling dynamics, revealing structured heterogeneity in cell populations.
Area of Science:
- Cellular Biology
- Systems Biology
- Biophysics
Background:
- Mammalian cell signaling exhibits significant cell-to-cell variability.
- The origins of this heterogeneity, whether stochastic fluctuations or distinct cellular states, remain unclear.
Purpose of the Study:
- To investigate the underlying structure of heterogeneity in mammalian cell signaling responses.
- To determine if distinct cellular states coexist within a population using calcium signaling as a model.
Main Methods:
- Utilized calcium response to adenosine trisphosphate as a model system.
- Applied a mechanistic dynamical systems model for a functional definition of cellular state.
- Employed Bayesian parameter inference for individual cell parameter fitting and clustering.
Main Results:
- Identified three distinct cellular states within the cell population through clustering of inferred parameters.
- Demonstrated that variability in inositol trisphosphate receptor (IP3R) response accounts for the majority of calcium heterogeneity.
- Confirmed predictions through experimental validation.
Conclusions:
- Observed cell-to-cell variability in signaling response arises from structured heterogeneity and distinct cellular states.
- Highlights the importance of single-cell parameter inference for uncovering hidden population structures.
- Emphasizes the role of IP3R dynamics in driving calcium signaling heterogeneity.
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