Iakovlev Mikhail, Faravelli Simone, Becskei Attila
Biozentrum, University of Basel, Basel, Switzerland.
Front Cell Dev Biol. 2021 Apr 29;9:642212. doi: 10.3389/fcell.2021.642212. eCollection 2021.
Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single-cell RNA-seq data with a simple metric. This metric can detect exclusivity independently of the mean value and the monoallelic nature of gene expression. Chromosomal segments and gene families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.
排他性随机基因选择将精确性与多样性相结合。这种调控使大多数T细胞能够精确表达从大量库中选择的一种T细胞受体异构体，并精确地对多种抗原作出反应。一些细胞表达两种受体异构体，揭示了这一过程的随机性。气味受体和原钙黏蛋白的类似调控分别使细胞能够识别气味并在神经元相互作用网络中赋予细胞个体性。我们通过用一个简单的指标分析单细胞RNA测序数据，探讨了其他家族的基因是否也有排他性表达。这个指标可以独立于基因表达的平均值和单等位基因性质来检测排他性。染色体片段和基因家族更有可能同时表达基因而非排他性表达，这可能是由于共享调控的进化和生物物理方面的原因。尽管如此，在多种细胞类型中都检测到了具有排他性基因选择的基因家族，其中大多数是参与离子运输和细胞黏附的膜蛋白，这表明了这两种功能的协调性。因此，随机排他性表达超出了典型家族的范围，使基因选择的精确性能够与细胞间相互作用的多样性相结合。
