Shimoni Chen, Goldstein Myah, Ribarski-Chorev Ivana, Schauten Iftach, Nir Dana, Strauss Carmit, Schlesinger Sharon
Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Front Cell Dev Biol. 2020 Sep 22;8:565970. doi: 10.3389/fcell.2020.565970. eCollection 2020.
Heat stress can have a serious impact on the health of both humans and animals. A major question is how heat stress affects normal development and differentiation at both the cellular and the organism levels. Here we use an experimental system to address how heat shock treatment influences the properties of bovine mesenchymal stem cells (MSCs)-multipotent progenitor cells-which are found in most tissues. Because cattle are sensitive to harsh external temperatures, studying the effects of heat shock on MSCs provides a unique platform to address cellular stress in a physiologically relevant model organism. Following isolation and characterization of MSCs from the cow's umbilical cord, heat shock was induced either as a pulse (1 h) or continuously (3 days), and consequent effects on MSCs were characterized. Heat shock induced extensive phenotypic changes in MSCs and dramatically curtailed their capacity to proliferate and differentiate. These changes were associated with a partial arrest in the G1/S or G2/M checkpoints. Furthermore, MSCs lost their ability to resolve the inflammatory response of RAW macrophages in coculture. A possible explanation for this loss of function is the accumulation of reactive oxygen species and malfunction of the mitochondria in the treated cells. Heat shock treatments resulted in stress-induced premature senescence, affecting the MSCs' ability to proliferate properly for many cell passages to follow. Exposure to elevated external temperatures leads to mitochondrial damage and oxidative stress, which in turn conveys critical changes in the proliferation, differentiation, and immunomodulatory phenotype of heat-stressed MSCs. A better understanding of the effect of heat shock on humans and animals may result in important health and economic benefits.
热应激会对人类和动物的健康产生严重影响。一个主要问题是热应激如何在细胞和机体水平上影响正常发育和分化。在此，我们使用一个实验系统来研究热休克处理如何影响牛间充质干细胞（MSCs）——一种存在于大多数组织中的多能祖细胞——的特性。由于牛对恶劣的外部温度敏感，研究热休克对MSCs的影响为在生理相关的模式生物中研究细胞应激提供了一个独特的平台。从牛脐带中分离并鉴定MSCs后，以脉冲方式（1小时）或持续方式（3天）诱导热休克，并对热休克后MSCs的后续影响进行表征。热休克诱导了MSCs广泛的表型变化，并显著削弱了它们的增殖和分化能力。这些变化与G1/S或G2/M检查点的部分阻滞有关。此外，MSCs在共培养中失去了化解RAW巨噬细胞炎症反应的能力。这种功能丧失的一个可能解释是处理过的细胞中活性氧的积累和线粒体的功能障碍。热休克处理导致应激诱导的早衰，影响MSCs在随后许多细胞传代中正常增殖的能力。暴露于升高的外部温度会导致线粒体损伤和氧化应激，进而导致热应激MSCs的增殖、分化和免疫调节表型发生关键变化。更好地了解热休克对人类和动物的影响可能会带来重要的健康和经济效益。
