Université Côte d'Azur, CNRS, INRAE, ISA, 06903 Sophia Antipolis, France.
Int J Mol Sci. 2020 Sep 2;21(17):6362. doi: 10.3390/ijms21176362.
Tissues must adapt to the different external stimuli so that organisms can survive in their environments. The intestine is a vital organ involved in food processing and absorption, as well as in innate immune response. Its adaptation to environmental cues such as diet and biotic/abiotic stress involves regulation of the proliferative rate and a switch of division mode (asymmetric versus symmetric) of intestinal stem cells (ISC). In this review, we outline the current comprehension of the physiological and molecular mechanisms implicated in stem cell division modes in the adult midgut. We present the signaling pathways and polarity cues that control the mitotic spindle orientation, which is the terminal determinant ensuring execution of the division mode. We review these events during gut homeostasis, as well as during its response to nutrient availability, bacterial infection, chemical damage, and aging. JNK signaling acts as a central player, being involved in each of these conditions as a direct regulator of spindle orientation. The studies of the mechanisms regulating ISC divisions allow a better understanding of how adult stem cells integrate different signals to control tissue plasticity, and of how various diseases, notably cancers, arise from their alterations.
组织必须适应不同的外部刺激，以使生物体能够在其环境中生存。肠道是参与食物加工和吸收以及先天免疫反应的重要器官。它对饮食和生物/非生物应激等环境线索的适应涉及到肠道干细胞（ISC）增殖率的调节和分裂模式（不对称与对称）的转换。在这篇综述中，我们概述了目前对成年中肠干细胞分裂模式所涉及的生理和分子机制的理解。我们介绍了控制有丝分裂纺锤体取向的信号通路和极性线索，这是确保执行分裂模式的最终决定因素。我们回顾了在肠道稳态期间，以及在其对营养物质可用性、细菌感染、化学损伤和衰老的反应过程中，这些事件的发生。JNK 信号转导作为一个核心参与者，作为纺锤体取向的直接调节剂，参与了所有这些条件。对调节 ISC 分裂的机制的研究，使我们能够更好地理解成年干细胞如何整合不同的信号来控制组织可塑性，以及各种疾病（特别是癌症）如何从它们的改变中产生。
