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

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Title: Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses
Authors: 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
Source: Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024)
Publisher Information: Nature Portfolio, 2024.
Publication Year: 2024
Collection: LCC:Science
Subject Terms: Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-024-48929-3
Access URL: https://doaj.org/article/7c21a45654ef495b9c4a5d11832b5d82
Accession Number: edsdoj.7c21a45654ef495b9c4a5d11832b5d82
Database: Directory of Open Access Journals
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  Data: 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.
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