| Title: | Reconstructing the regulatory circuit of cell fate determination in yeast mating response |
| Author(s): | Shao B; Yuan H; Zhang R; Wang X; Zhang S; Ouyang Q; Hao N; Luo C; |
| Address: | "Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China. School of Informatics and Computing, Indiana University, Bloomington, Indiana, United States of America. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, California, United States of America" |
| DOI: | 10.1371/journal.pcbi.1005671 |
| ISSN/ISBN: | 1553-7358 (Electronic) 1553-734X (Print) 1553-734X (Linking) |
| Abstract: | "Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized. To understand the gene regulatory networks that control this differentiation switch, we employed a high-throughput microfluidic imaging system that allows real-time and simultaneous measurements of cell growth and protein expression. Using kinetic modeling of protein dynamics, we classified the stimulus-dependent changes in protein abundance into two sources: global changes due to physiological alterations and gene-specific changes. A quantitative framework was proposed to decouple gene-specific regulatory modes from the growth-dependent global modulation of protein abundance. Based on the temporal patterns of gene-specific regulation, we established the network architectures underlying distinct cell fates using a reverse engineering method and uncovered the dose-dependent rewiring of gene regulatory network during mating differentiation. Furthermore, our results suggested a potential crosstalk between the pheromone response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis pathway, which might underlie a cell differentiation switch in yeast mating response. In summary, our modeling approach addresses the distinct impacts of the global and gene-specific regulation on the control of protein dynamics and provides new insights into the mechanisms of cell fate determination. We anticipate that our integrated experimental and modeling strategies could be widely applicable to other biological systems" |
| Keywords: | "Gene Regulatory Networks/*genetics *Models, Biological Pheromones/*genetics Proteomics *Saccharomyces cerevisiae/cytology/genetics/physiology Saccharomyces cerevisiae Proteins/genetics/metabolism;" |
| Notes: | "MedlineShao, Bin Yuan, Haiyu Zhang, Rongfei Wang, Xuan Zhang, Shuwen Ouyang, Qi Hao, Nan Luo, Chunxiong eng R01 GM111458/GM/NIGMS NIH HHS/ 2017/07/26 PLoS Comput Biol. 2017 Jul 24; 13(7):e1005671. doi: 10.1371/journal.pcbi.1005671. eCollection 2017 Jul" |
