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Mathematical modeling reveals the mechanisms of feedforward regulation in cell fate decisions in budding yeast

Frontiers of Electrical and Electronic Engineering in China 2015年第2期10卷 55-68页

作者： Wenlong Li Ming Yi Xiufen Zou School of Mathematics and Statistics Wuhan University Wuhan 430072 China Key Laboratory of Magnetic Resonance in Biological Systems Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan 430071 China Department of Physics College of Science Huazhong Agricultural University Wuhan 430070 China

The determination of cell fate is one of the key questions of developmental biology. Recent experiments showed that feedforward regulation is a novel feature of regulatory networks that controls reversible cellular transitions. However, the underlying mechanism of feedforward regulation-mediated cell fate decision is still unclear. Therefore, using experimental data, we develop a full mathematical model of the molecular network responsible for cell fate selection in budding yeast. To validate our theoretical model, we first investigate the dynamical behaviors of key proteins at the Start transition point and the G1/S transition point; a crucial three-node motif consisting of cyclin （Clnl/2）, Substrate/Subunit Inhibitor of cyclin-dependent protein kinase （Sic1） and cyclin B （C165/6） is considered at these points. The rapid switches of these important components between high and low levels at two transition check points are demonstrated reasonably by our model. Many experimental observations about cell fate decision and cell size control are also theoretically reproduced. Interestingly, the feedforward regulation provides a reliable separation between different cell fates. Next, our model reveals that the threshold for the amount of WHiskey OVhi5） removed from the nucleus is higher at the Reentry point in pheromone-arrested cells compared with that at the Start point in cycling cells. Furthermore, we analyze the hysteresis in the cell cycle kinetics in response to changes in pheromone concentration, showing that Cln3 is the primary driver of reentry and Clnl/2 is the secondary driver of reentry. In particular, we demonstrate that the inhibition of C1nl/2 due to the accumulation of Factor ARrest （Far1） directly reinforces arrest. Finally, theoretical work verifies that the three-node coherent feedforward motif created by cell FUSion （Fus3）, Farl and STErile （Stel2） ensures the rapid arrest and reversibility of a cellular state. The combination of our theoretical model

关键词： cell fate decision feedforward mechanism mathematical modeling hysteresis reversibility

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Induced Pluripotency for Translational Research

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Genomics, Proteomics & Bioinformatics 2013年第5期11卷 288-293页

作者： Menghua Wu Guilai Chen Baoyang Hu State Key Laboratory of Reproductive Biology and Key Laboratory of Translational Stem cell Research Institute of ZoologyChinese Academy of Sciences

The advent of induced pluripotent stem cells （iPSCs） has revolutionized the concept of cellular reprogramming and potentially will solve the immunological compatibility issues that have so far hindered the application of human pluripotent stem cells in regenerative medicine. Recent findings showed that pluripotency is defined by a state of balanced lineage potency, which can be artificially instated through various procedures, including the conventional Yamanaka strategy. As a type of pluripotent stem cell, iPSCs are subject to the usual concerns over purity of differen- tiated derivatives and risks of tumor formation when used for cell-based therapy, though they pro- vide certain advantages in translational research, especially in the areas of personalized medicine, disease modeling and drug screening, iPSC-based technology, human embryonic stem cells （hESCs） and direct lineage conversion each will play distinct roles in specific aspects of translational medi- cine, and continue yielding surprises for scientists and the public.

关键词： iPSCs Pluripotency cell fate decision Translational medicine

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ROS regulated reversible protein phase separation synchronizes plant flowering

ROS regulated reversible protein phase separation synchroniz...

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2021年全国生物相分离和相变学术研讨会

作者： Cao Xu Institute of Genetics and Developmental Biology Chinese Academy of Sciences

How aerobic organisms exploit inevitably generated but potentially dangerous reactive oxygen species(ROS) to benefit nor-mal life is a fundamental biological *** accumulated ROS have been reported to prime stem cell ***,the underlying molecular mechanism is ***,we reveal that developmentally produced H O in plant shoot apical meristem(SAM)triggers reversible protein phase separation of TERMINATING FLOWER(TMF),a transcription factor that times flowering transition in the tomato by repressing pre-maturation of *** residues within TMF sense cellular redox to form disulfide bonds that concatenate multiple TMF molecules and elevate the amount of intrinsically disordered regions to drive phase *** triggered phase separation enables TMF to bind and sequester the promoter of a floral identity gene ANANTHA to repress its *** reversible transcriptional condensation via redox-regulated phase separation endows aerobic organisms with the flexibility of gene control in dealing with developmental cues.

关键词： ROS Phase separation redox stem cell cell fate decision transcriptional condensates

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