Open Access Highly Accessed Research article

Probing the role of stochasticity in a model of the embryonic stem cell – heterogeneous gene expression and reprogramming efficiency

Vijay Chickarmane2, Victor Olariu1 and Carsten Peterson13*

Author Affiliations

1 Computational Biology & Biological Physics, Lund University, Lund, Sweden

2 Division of Biology, California Institute of Technology, , Pasadena, USA

3 Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden

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BMC Systems Biology 2012, 6:98  doi:10.1186/1752-0509-6-98

Published: 13 August 2012

Additional files

Additional file 1:

Figure S1. Steady state analysis of the stem cell circuit as functions of LIF and I3concentrations. The dashed lines indicate unstable states. (A) The steady state values of NANOG, OCT4-SOX2 and G as functions of LIF concentration. The plots display two states of the cell. (i) the stem cell state – high OCT4-SOX2/NANOG and low G and (ii) the differentiated state with low OCT4-SOX2/NANOG and high G (B) Similar graphs for small molecule differentiation inhibitors I3 concentration (here for 100). Although there are still two states, NANOG is still higher here than in the previous case. Shown also is the level of FGF4 (magenta), which is at ≃20, which is much lower than in the previous case.

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Additional file 2:

Figure S2. NANOG mean and standard deviation as a function of the concentration of 2i/3i (LIF=0) computed using the LNA. In the upper panel, the mean value of NANOG , and the lower panel shows the standard deviation of NANOG. Also indicated as a red dashed line is the standard deviation of OCT4 which does not vary with 2i/3i.

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Additional file 3:

Figure S3. Time series of [N] and [OS] for the stochastic dynamics of the alternative architecture with no differentiation gene G for LIF=100. A differentiation event; NANOG (red) and OCT4-SOX2 (blue). The OCT4-SOX2 expression is not lost in a differentiated cell in the model without G.

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Additional file 4:

An architecture with no differentiation gene G.

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