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. 2017 Aug 3;3:19. doi: 10.1038/s41540-017-0020-5

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — Simpler network models demonstrating bistability of Nanog. a Scheme of simplified network, composed of core factors Nanog, Oct4, Sox2; Fgf4/Erk, β-catenin and Tcf3 are added to account for the inputs (i.e., PD and Chiron (CH), the two inhibitors present in 2i/LIF). Solid and dashed lines indicate transcriptional and non-transcriptional interactions, respectively. b, c Continuation of Nanog steady-state for the deterministic system (no noise) in serum/LIF (b) and 2i/LIF (c). Blue lines are stable steady states, while red lines are unstable. The maximal transcription rate, s ₄ (dotted black line), intersects both NH and NL steady-states, indicating bistability in serum/LIF (b), but is close to the saddle-node bifurcation in 2i/LIF (c). d Scheme of Nanog auto-inhibitory simplified network, with additional activation of β-catenin by Nanog. e, f Continuation of Nanog steady-state for the deterministic system (no noise) in serum/LIF (e) and 2i/LIF (f). Blue lines are stable steady-states, while red lines are unstable. The maximal transcription rate of Nanog auto-inhibition, s ₄ (dotted black line), intersects both NH and NL steady-states, indicating bistability in serum/LIF (e), while being closer to the saddle-node bifurcation in 2i/LIF (f). g Scheme of Nanog auto-inhibitory simplified network, with additional positive feedback supplied via an extra factor, i.e. Rest. h, i Continuation of Nanog steady-state for the deterministic system (no noise) in serum/LIF (h) and 2i/LIF (i). Blue lines are stable steady-states, while red lines are unstable. The maximal transcription rate of Rest activation on Nanog, s₆ (dotted black line), intersects both NH and NL steady-states, indicating bistability, in serum/LIF (h), and is very close to the saddle-node bifurcation in 2i/LIF (i)