Hyperthermia differentially affects specific human stem cells and their differentiated derivatives

The human body operates optimally at a core temperature of 37 degrees Celsius. Homeostasis at this temperature is essential for cellular and physiological functions (Cheshire, 2016). However, infectious diseases, inflammation, injury, neoplasia, and elevated climate temperature can cause a regulated rise in body core temperature, i.e., fever (Pasikhova et al., 2017). Indeed, an acute or chronic increase in temperature leads to detrimental effects on vasculature by altering a number of indices of vascular structure and function (DuBose et al., 1998). In addition, fever during pregnancy has been associated with an increased risk of neurodevelopmental impairment and congenital heart disease in offspring (White et al., 2007; Xia et al., 2019). An in-depth understanding of the cellular and molecular responses to febrile temperature in major body organs and tissues is, therefore, of scientific and clinical importance. Here, we construct a systematic, transcriptional atlas of fever-range heat stress across pluripotent and adult stem cells as well as their derivatives. Using this approach, we identify the cell types that are most susceptible or resistant to heat stress, as well as the fever-induced changes in gene expression. Our data provide a useful resource as well as potential biomarkers and therapeutic targets for the diagnosis and treatment of fever-associated disorders.