Toggle Switches (Okawa et al.)
Okawa S, Nicklas S, Zickenrott S, Schwamborn JC, Del Sol A
2016 · Stem cell reports
Identification of cell-fate determinants for directing stem cell differentiation remains a challenge.
Abstract
From the original paper, Stem cell reports · PubMed
Identification of cell-fate determinants for directing stem cell differentiation remains a challenge. Moreover, little is known about how cell-fate determinants are regulated in functionally important subnetworks in large gene-regulatory networks (i.e., GRN motifs). Here we propose a model of stem cell differentiation in which cell-fate determinants work synergistically to determine different cellular identities, and reside in a class of GRN motifs known as feedback loops. Based on this model, we develop a computational method that can systematically predict cell-fate determinants and their GRN motifs. The method was able to recapitulate experimentally validated cell-fate determinants, and validation of two predicted cell-fate determinants confirmed that overexpression of ESR1 and RUNX2 in mouse neural stem cells induces neuronal and astrocyte differentiation, respectively. Thus, the presented GRN-based model of stem cell differentiation and computational method can guide differentiation experiments in stem cell research and regenerative medicine.
Summary
Editorial summary pending review by the maintainer. The paper's own abstract appears above; the Atlas summary in the maintainer's voice will explain how Toggle Switches (Okawa et al.) relates to the cross-modality inverse-design framework of the review.
Why this level
Level 3 because candidate interventions enter an explicit forward operator and the predicted post-intervention outcome is what scores each candidate. Representation family is executable intervention model. Cited in §3.4 of the review. Editorial rationale pending review by the maintainer.