Reconstructing the regulatory circuit of cell fate determination in yeast mating response.
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-07-01
|
| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5546706?pdf=render |
| _version_ | 1819041869145833472 |
|---|---|
| author | Bin Shao Haiyu Yuan Rongfei Zhang Xuan Wang Shuwen Zhang Qi Ouyang Nan Hao Chunxiong Luo |
| author_facet | Bin Shao Haiyu Yuan Rongfei Zhang Xuan Wang Shuwen Zhang Qi Ouyang Nan Hao Chunxiong Luo |
| author_sort | Bin Shao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T09:31:51Z |
| format | Article |
| id | doaj.art-cb1d27e45f544884bce72f5e6d9ed319 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-21T09:31:51Z |
| publishDate | 2017-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-cb1d27e45f544884bce72f5e6d9ed3192022-12-21T19:08:44ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-07-01137e100567110.1371/journal.pcbi.1005671Reconstructing the regulatory circuit of cell fate determination in yeast mating response.Bin ShaoHaiyu YuanRongfei ZhangXuan WangShuwen ZhangQi OuyangNan HaoChunxiong LuoMassive 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.http://europepmc.org/articles/PMC5546706?pdf=render |
| spellingShingle | Bin Shao Haiyu Yuan Rongfei Zhang Xuan Wang Shuwen Zhang Qi Ouyang Nan Hao Chunxiong Luo Reconstructing the regulatory circuit of cell fate determination in yeast mating response. PLoS Computational Biology |
| title | Reconstructing the regulatory circuit of cell fate determination in yeast mating response. |
| title_full | Reconstructing the regulatory circuit of cell fate determination in yeast mating response. |
| title_fullStr | Reconstructing the regulatory circuit of cell fate determination in yeast mating response. |
| title_full_unstemmed | Reconstructing the regulatory circuit of cell fate determination in yeast mating response. |
| title_short | Reconstructing the regulatory circuit of cell fate determination in yeast mating response. |
| title_sort | reconstructing the regulatory circuit of cell fate determination in yeast mating response |
| url | http://europepmc.org/articles/PMC5546706?pdf=render |
| work_keys_str_mv | AT binshao reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT haiyuyuan reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT rongfeizhang reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT xuanwang reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT shuwenzhang reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT qiouyang reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT nanhao reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse AT chunxiongluo reconstructingtheregulatorycircuitofcellfatedeterminationinyeastmatingresponse |