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细胞在噪音影响下的分化 PNAS

已有 3662 次阅读 2014-3-14 02:15 |个人分类:科研笔记|系统分类:科研笔记| 合成生物学

这是我第一篇生物的文章,去年5月份接收的。我们利用合成生物学的技术,研究了细胞是在噪音影响下分化的过程。

http://www.pnas.org/content/110/26/10610.short

 

Both microbes and multicellular organisms actively regulate their cell fate determination to cope with changing environments or to ensure proper development. Here, we use synthetic biology approaches to engineer bistable gene networks to demonstrate that stochastic and permanent cell fate determination can be achieved through initializing gene regulatory networks (GRNs) at the boundary between dynamic attractors. We realize this experimentally by linking a synthetic GRN to a natural output of galactose metabolism regulation in yeast. Combining mathematical modeling and flow cytometry, we show that our engineered systems are bistable and that inherent gene expression stochasticity does not induce spontaneous state transitioning at steady state. Mathematical analysis predicts that stochastic cell fate determination in this case can only be realized when gene expression fluctuation occurs on or near attractor basin boundaries (the points of instability). Guided by numerical simulations, experiments are designed and performed with quantitatively diverse gene networks to test model predictions, which are verified by both flow cytometry and single-cell microscopy. By interfacing rationally designed synthetic GRNs with background gene regulation mechanisms, this work investigates intricate properties of networks that illuminate possible regulatory mechanisms for cell differentiation and development that can be initiated from points of instability.

PNAS-2013-Wu-10610-5.pdf


九月份的时候另外一个组做了和我们很类似的工作,也在pnas上

http://www.pnas.org/content/111/3/972.short

他们进一步讨论了如果控制细胞分化的比例。

 



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