Abstract
Human induced pluripotent stem cells (hiPSCs) are highly sensitive to extrinsic physical and biochemical signals from their extracellular microenvironments. In this study, we analyzed the effect of cyclic temperature changes on hiPSCs behaviors, especially by means of scanning force microscopy (BIO-AFM). The alternation in cellular mechanics, as well as the secretion and pattern of deposition of extracellular matrix (ECM) protein in hiPSCs were evaluated. The arrangement of the actin cytoskeleton changed with the variation of the temperature. The rearranged cytoskeleton architecture led to the subsequent changes in cell mechanics (Young's modulus of hiPSCs). With the exposure to the cyclic cold stimuli, an increase in the average surface roughness (Ra) and roughness mean square (RMS) was detected. This observation might be at least in part due to the upregulated secretion of Laminin α5 during repeated temporary cooling. The expression of pluripotent markers, NANOG and SOX2, was not impaired in hiPSCs, when exposed to the cyclic cold stimuli for 24 h. Our findings provide an insight into the effect of temperature on the hiPSC behaviors, which may contribute to a better understanding of the application of locally controlled therapeutic hypothermia.Graphic abstractThe cyclic temperature changes, from 37 to 10 °C, rapidly increased the mechanical strength of human-induced pluripotent stem cells (hiPSCs), which could be explained by the re-arrangement of cytoskeletons. The capacity of hiPSCs to remodel the extracellular matrix was also altered by the repeated temporary cooling, as they exhibit an enhanced ability to physically remodulate and secrete the ECM components.
Highlights
Human induced pluripotent stem cells-based models are promising tools for the investigation of stem cell fate and the development of patient-specific diseases models [1, 2]
Actin filament (F-actin) is one of the main types of cytoskeletal polymers, which regulates cell shape, mechanical properties, and intracellular signaling transduction [37]. In both groups, thick F-actin fibers were displayed in parallel to the colony edge of Human induced pluripotent stem cells (hiPSCs), while a stronger fluorescence signal was detected in the hiPSC colony exposed to the cyclic temperature changes (Fig. 2a)
At the single-cell level, more filopodia that formed by the long tight bundles of F-actin were observed in hiPSCs treated with the repeated temporary cooling
Summary
Human induced pluripotent stem cells (hiPSCs)-based models are promising tools for the investigation of stem cell fate and the development of patient-specific diseases models [1, 2] In their extracellular environment, hiPSCs are exposed to multiple mechanical stimuli that regulate their fate [3,4,5]. HiPSCs are able to adapt to those stresses and prevent themselves from damage [6, 7]. Another important stress response of the cells is the thermal response [14, 15].
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