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Abstract
Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).
A spatial transcriptomics and single-cell multiomics study performed on mouse brain tissue. Here, authors show region-specific spaceflight-induced alterations in processes of neurogenesis, synaptogenesis and synaptic transmission.
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1 KTH Royal Institute of Technology, Science for Life Laboratory, Department of Gene Technology, Stockholm, Sweden (GRID:grid.5037.1) (ISNI:0000000121581746)
2 NASA Ames Research Center, Space Biosciences Division, Mountain View, USA (GRID:grid.419075.e) (ISNI:0000 0001 1955 7990)
3 Science for Life Laboratory, National Bioinformatics Infrastructure Sweden, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden (GRID:grid.452834.c) (ISNI:0000 0004 5911 2402)
4 Uppsala University, Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
5 Bioquant, Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373)
6 Bioquant, Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373); Cellzome, GSK, Heidelberg, Germany (GRID:grid.420105.2) (ISNI:0000 0004 0609 8483)
7 NASA Ames Research Center, Space Biosciences Division, Mountain View, USA (GRID:grid.419075.e) (ISNI:0000 0001 1955 7990); Bionetics, Yorktown, USA (GRID:grid.423411.1) (ISNI:0000 0004 0593 4443)
8 The Children’s Hospital of Philadelphia Research Institute, Department of Biomedical and Health Informatics, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770)
9 NASA Ames Research Center, KBR, Space Biosciences Division, Mountain View, USA (GRID:grid.481680.3) (ISNI:0000 0004 0634 8729)
10 KTH Royal Institute of Technology, Science for Life Laboratory, Department of Gene Technology, Stockholm, Sweden (GRID:grid.5037.1) (ISNI:0000000121581746); Karolinska Institute, Department of Cell and Molecular Biology, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
11 Biomedicum, Department of Neuroscience, Karolinska Institutet, Solna, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
12 NASA Ames Research Center, NASA Postdoctoral Program - Oak Ridge Associated Universities, Mountain View, USA (GRID:grid.419075.e) (ISNI:0000 0001 1955 7990)
13 Karolinska Institute, Department of Cell and Molecular Biology, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Department of Pharmacology and Toxicology University Medical Center Goettingen, Pharmacology and Toxicology, Goettingen, Germany (GRID:grid.411984.1) (ISNI:0000 0001 0482 5331)
14 The Children’s Hospital of Philadelphia Research Institute, Department of Biomedical and Health Informatics, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770); The University of Pennsylvania Perelman School of Medicine, Department of Pediatrics, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
15 The University of Pennsylvania Perelman School of Medicine, Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia and Department of Pediatrics, Division of Human Genetics, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
16 Karolinska Institute, Department of Medicine, Huddinge, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)