Space associated stem cell hallmarks of aging (SASHA) in astronauts
Abstract
Abstract Previous reports revealed immune dysfunction, chromosomal abnormalities, cytokine deregulation, and telomere length dynamics following prolonged spaceflight. However, the stress of space on hematopoietic stem and progenitor cells (HSPCs) that maintain lifelong hematopoiesis and immune responses was not studied. We performed HSPC functionally organized multi-omics aging (HSPC-FOMA) analyses in 7 astronauts before, during, and after short-duration ISS missions. Specifically, whole genome sequencing with telomere length, mitochondrial and clonal mutational profiling; whole transcriptome sequencing with RNA editing and retrotransposon analyses; single-cell RNA sequencing; cytokine arrays; and FACS-analyses were performed to assess HSPC and immune subpopulation survival dynamics. Overall, the observed space-associated stem cell hallmarks of aging, including spaceflight-dependent alterations in HSPC survival and self-renewal, adenosine deaminase associated with RNA1 (ADAR1), telomere maintenance, mobilization and cell cycle gene expression combined with space-associated clonal hematopoietic mutations, apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3C) activation and retrotransposon deregulation warrant countermeasure development to enable long-duration spaceflight.
Article Details
Authors (20)
Jessica Pham
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Shuvro Nandi
1UC San Diego, Medicine, La Jolla, United States
Larissa Balaian
1UC San Diego, Medicine, La Jolla, United States
Claire Engstrom
1UC San Diego, Medicine, La Jolla, United States
Patrick Chang
2Sanford Stem Cell Institute, UC San Diego, La Jolla, United States
Karla Mack
2Sanford Stem Cell Institute, UC San Diego, La Jolla, United States
Inge Van Der Werf
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Emma Klacking
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Jenna Sneifer
1UC San Diego, Medicine, La Jolla, United States
Neha Katragadda
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Kendale Wirtjes
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Antonio Ruiz
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Daisy Chilin-Fuentes
Elsa Molina
4The Salk Institute for Biological Studies, Next Generation Sequencing Core, La Jolla, United States
Pinar Mesci
Jana Stoudemire
2Sanford Stem Cell Institute, UC San Diego, La Jolla, United States
Sheldon Morris
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States
Thomas Whisenant
Ludmil Alexandrov
3UCSD, Department of Cellular and Molecular Medicine, Department of Bioengineering, La Jolla, United States
Catriona Jamieson
1Sanford Stem Cell Institute, UCSD, Division of Regenerative Medicine, Departemnt of Medicine, La Jolla, United States