Parabolic flight-induced gravity variations initiate acute functional and transcriptional responses in cardiac organoids

Abstract Changes of gravity induce profound cardiovascular adaptations in astronauts during spaceflights. Yet the early physiological mechanisms initiating cardiac remodeling remain unclear, as most studies have focused on long-duration spaceflight adaptations. Here, we investigated early functional and molecular responses using three-dimensional cardiac organoids derived from mouse embryonic stem cells exposed to altered gravity during the 69th CNES (Centre National d’Etudes Spatiales) parabolic flight campaign. Cardiac organoids were exposed to 31 consecutive parabola comprising repeated microgravity and hypergravity phases, followed by immediate functional and transcriptomic analyses after the flight. In this study, parabolic flight-induced gravity variations were associated with maturation-dependent adaptations, increased cardiac beating rate and modified calcium dynamics. Transcriptomic analyses revealed modifications of gene expressions involved in calcium homeostasis, mitochondrial function and stress-related pathways, including upregulation of S100g , Ifi27l2a , Prelid2 , Spink1 and Apom . Together, these findings support the use of cardiac organoids and parabolic flight as a complementary research platform to investigate early functional and molecular mechanisms of cardiac adaptation to gravity variation.