Mouse embryonic stem cells embody organismal level cold resistance. Suita K et al.
Raw data and codes in the following study. The commons folder including the shared codes used throughout the analysis is included in the Figure1.zip. During hibernation, some mammals show low body temperatures (< 10 °C). Tissues from such hibernators exhibit cold resistance even when the animal is not hibernating. Mice can also enter hypothermic fasting-induced torpor (FIT), but the cold resistance of FIT has never been related to their tissues. Here, we show that an inbred mouse STM2 exhibits lower body temperature during FIT than C57BL/6J or MYS/Mz. Thus, STM2 resists the cold more than other strains. A strain-specific mouse embryonic stem (ES) cell proved that STM2 ES cells are more cold-resistant than others. Pharmacological intervention and transcriptome analysis suggest that STM2 ES cells rely on the oxidative phosphorylation (OXPHOS) pathway but respire independently of the electron transfer chain complex I in the cold. We also found that the liver of STM2 uses OXPHOS more in cold than other strains. This study demonstrates that an organismal phenotype of torpor can be studied in an in vitro setup using mouse cells. Figure 1 | STM2 shows lower body temperature at fasting-induced torpor. Figure 2 | ES cell–establishment from mouse inbred strains. Figure 3 | The metabolic pathway preference of STM2 ES cells is unchanged under low temperatures. Figure 4 | STM2 ES cells own a temperature-insensitive complex I–independent respiration. Figure 5 | Transcriptome analysis of cold-cultured ES cells reveals STM2 has suppressed expression of the CI–related genes. Figure 6 | STM2 tissues show cold-resistance.
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All data analysis and figure production was done by R. See the manuscript for details.