MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity
MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity
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DOI：
10.1021/acs.jpcb.7b04774
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发表时间：
2017-08-17
影响因子：
3.3
通讯作者：
Mafe, Salvador
中科院分区：
文献类型：
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作者：
Cervera, Javier;Meseguer, Salvador;Mafe, Salvador
我们从理论上研究了microRNA（miRNA）通过电压门控间隙连接的细胞间转移。而不是一个特定的系统建模，我们使用一个通用的方法来描述遗传机制和单细胞电位之间的相互作用。在不同的条件下，包括空间不均匀的转录速率和局部细胞间转移的miRNA的多细胞系综的动力学进行了模拟。这些过程导致miRNA、mRNA和离子通道蛋白浓度的时空变化，由于电势的整体平均性质，这些变化最终改变小的多细胞结构域的生物电状态。模拟允许一个定性的理解时，观察到的特定信号分子通过间隙连接转移的影响的上下文依赖性。结果表明，有效的miRNA细胞间转移可以通过将单细胞遗传和生物电状态转化为受差距连接相互连接性调节的多细胞状态来实现对小细胞结构域的时空控制。
We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially inhomogeneous transcription rates and local intercellular transfer of miRNAs. These processes result in spatiotemporal changes of miRNA, mRNA, and ion channel protein concentrations that eventually modify the bioelectrical states of small multicellular domains because of the ensemble average nature of the electrical potential. The simulations allow a qualitative understanding of the context-dependent nature of the effects observed when specific signaling molecules are transferred through gap junctions. The results suggest that an efficient miRNA intercellular transfer could permit the spatiotemporal control of small cellular domains by the conversion of single-cell genetic and bioelectric states into multicellular states regulated by the gap junction interconnectivity.