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Updated: Mar 16, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
A Generalized Gene-Regulatory Network Model of Stem Cell Differentiation for Predicting Lineage Specifiers
Satoshi Okawa1, Sarah Nicklas2, Sascha Zickenrott1
1Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
Abstract:
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.
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