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 and Christopher E. Mason ()
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Kirill Grigorev: Weill Cornell Medicine
Theodore M. Nelson: Columbia University Irving Medical Center
Eliah G. Overbey: Weill Cornell Medicine
Nadia Houerbi: Weill Cornell Medicine
JangKeun Kim: Weill Cornell Medicine
Deena Najjar: Weill Cornell Medicine
Namita Damle: Weill Cornell Medicine
Evan E. Afshin: Weill Cornell Medicine
Krista A. Ryon: Weill Cornell Medicine
Jean Thierry-Mieg: NIH
Danielle Thierry-Mieg: NIH
Ari M. Melnick: Weill Cornell Medicine
Jaime Mateus: Space Exploration Technologies Corporation (SpaceX)
Christopher E. Mason: Weill Cornell Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48929-3

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