A logic-incorporated gene regulatory network deciphers principles in cell fate decisions

作者：Gang Xue, Xiaoyi Zhang, Wanqi Li, Lu Zhang, Zongxu Zhang, Xiaolin Zhou, Di Zhang, Lei Zhang, Zhiyuan Li · 发表于：eLife · 年份：2024 · DOI：10.7554/elife.88742.3 · 被引用次数：15 · 研究领域：Gene Regulatory Network Analysis、Single-cell and spatial transcriptomics、CRISPR and Genetic Engineering

Organisms utilize gene regulatory networks (GRN) to make fate decisions, but the regulatory mechanisms of transcription factors (TF) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven). Under the noise-driven mode, we distilled the relationship among fate bias, regulatory logic, and noise profile. Under the signal-driven mode, we bridged regulatory logic and progression-accuracy trade-off, and uncovered distinctive trajectories of reprogramming influenced by logic motifs. In differentiation, we characterized a special logic-dependent priming stage by the solution landscape. Finally, we applied our findings to decipher three biological instances: hematopoiesis, embryogenesis, and trans-differentiation. Orthogonal to the classical analysis of expression profile, we harnessed noise patterns to construct the GRN corresponding to fate transition. Our work presents a generalizable framework for top-down fate-decision studies and a practical approach to the taxonomy of cell fate decisions.