Transcriptional Regulation of Lineage Commitment - A Stochastic Model of Cell Fate Decisions
Figure 5
Expression of Gata2 defines regions of high and low commitment probability.
(A) Simulated gene expression time-course for Gata1 (red), Gata2 (blue) and Mpo (green) and corresponding probability of commitment (grey). Probability of commitment is very low for most of the time-course, punctuated with high probability peaks for specific gene expression combinations. (B) Gata1, Gata2 and Mpo expressions of 160 simulated cells at the moment of commitment transition (in silico CP, grey) compared to expressions in experimental self-renewing (experimental SR, blue) and committed progenitor cells (experimental CP1, yellow). Absence of Gata2 expression defines a commitment-impeded region where no commitment events could be observed either experimentally or in simulations; expression of Gata2 defines a commitment-permissive region where commitment can happen through multiple gene expression combinations: Gata2 ON / Gata1 ON / Mpo ON (I), Gata2 ON / Gata1 OFF / Mpo ON (II), Gata2 ON / Gata1 OFF / Mpo OFF (III), Gata2 ON / Gata1 ON / Mpo OFF (IV). Instances of in silico commitment events through each scenario are presented in Figure S4. (C) Simulated gene expression profile leading into a commitment event: the commitment-impeded region is initially visited (Gata2 OFF), followed by different combinations within the commitment-permissive region (sequentially II, I and IV), with commitment ultimately taking place with Gata2 ON / Gata1 ON / Mpo OFF.