Nature Communications (Jun 2024)

Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses

  • Kirill Grigorev,
  • Theodore M. Nelson,
  • Eliah G. Overbey,
  • Nadia Houerbi,
  • JangKeun Kim,
  • Deena Najjar,
  • Namita Damle,
  • Evan E. Afshin,
  • Krista A. Ryon,
  • Jean Thierry-Mieg,
  • Danielle Thierry-Mieg,
  • Ari M. Melnick,
  • Jaime Mateus,
  • Christopher E. Mason

DOI
https://doi.org/10.1038/s41467-024-48929-3
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 11

Abstract

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Abstract The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m6A methylation profiles for a human space mission, suggesting a significant spike in m6A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome’s dynamic response to spaceflight.