Abadie Kathleen, Pease Nicholas A, Wither Matthew J, Kueh Hao Yuan
Department of Bioengineering, University of Washington.
Molecular and Cellular Biology Program, University of Washington.
Curr Opin Syst Biol. 2019 Dec;18:95-103. doi: 10.1016/j.coisb.2019.10.013. Epub 2019 Nov 16.
To protect against diverse challenges, the immune system must continuously generate an arsenal of specialized cell types, each of which can mount a myriad of effector responses upon detection of potential threats. To do so, it must generate multiple differentiated cell populations with defined sizes and proportions, often from rare starting precursor cells. Here, we discuss the emerging view that inherently probabilistic mechanisms, involving rare, rate-limiting regulatory events in single cells, control fate decisions and population sizes and fractions during immune development and function. We first review growing evidence that key fate control points are gated by stochastic signaling and gene regulatory events that occur infrequently over decision-making timescales, such that initially homogeneous cells can adopt variable outcomes in response to uniform signals. We next discuss how such stochastic control can provide functional capabilities that are harder to achieve with deterministic control strategies, and may be central to robust immune system function.
为抵御各种挑战，免疫系统必须持续生成一系列专门的细胞类型，每种细胞在检测到潜在威胁时都能引发无数种效应反应。为此，它必须经常从稀少的起始前体细胞中生成具有确定大小和比例的多个分化细胞群体。在此，我们讨论一种新出现的观点，即内在概率机制，涉及单细胞中罕见的、限速调节事件，在免疫发育和功能过程中控制命运决定以及群体大小和比例。我们首先回顾越来越多的证据表明，关键的命运控制点由随机信号传导和基因调节事件控制，这些事件在决策时间尺度上很少发生，以至于最初同质的细胞在面对统一信号时可采用可变的结果。接下来，我们讨论这种随机控制如何提供确定性控制策略难以实现的功能能力，并且可能是强大免疫系统功能的核心。
