Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development

Sherina Malkani; Christopher R Chin; Egle Cekanaviciute; Marie Mortreux; Hazeem Okinula; Marcel Tarbier; Ann-Sofie Schreurs; Yasaman Shirazi-Fard; Candice G T Tahimic; Deyra N Rodriguez; Brittany S Sexton; Daniel Butler; Akanksha Verma; Daniela Bezdan; Ceyda Durmaz; Matthew MacKay; Ari Melnick; Cem Meydan; Sheng Li; Francine Garrett-Bakelman; Bastian Fromm; Ebrahim Afshinnekoo; Brad W Langhorst; Eileen T Dimalanta; Margareth Cheng-Campbell; Elizabeth Blaber; Jonathan C Schisler; Charles Vanderburg; Marc R Friedländer; J Tyson McDonald; Sylvain V Costes; Seward Rutkove; Peter Grabham; Christopher E Mason; Afshin Beheshti

doi:10.1016/j.celrep.2020.108448

Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development

Cell Rep. 2020 Dec 8;33(10):108448. doi: 10.1016/j.celrep.2020.108448. Epub 2020 Nov 25.

Authors

Sherina Malkani¹, Christopher R Chin², Egle Cekanaviciute³, Marie Mortreux⁴, Hazeem Okinula⁵, Marcel Tarbier⁶, Ann-Sofie Schreurs⁷, Yasaman Shirazi-Fard³, Candice G T Tahimic⁷, Deyra N Rodriguez⁸, Brittany S Sexton⁸, Daniel Butler², Akanksha Verma², Daniela Bezdan⁹, Ceyda Durmaz², Matthew MacKay², Ari Melnick¹⁰, Cem Meydan², Sheng Li¹¹, Francine Garrett-Bakelman¹², Bastian Fromm⁶, Ebrahim Afshinnekoo¹³, Brad W Langhorst⁸, Eileen T Dimalanta⁸, Margareth Cheng-Campbell¹⁴, Elizabeth Blaber¹⁵, Jonathan C Schisler¹⁶, Charles Vanderburg¹⁷, Marc R Friedländer⁶, J Tyson McDonald¹⁸, Sylvain V Costes³, Seward Rutkove⁴, Peter Grabham⁵, Christopher E Mason¹⁹, Afshin Beheshti²⁰

Affiliations

¹ Blue Marble Space Institute of Science, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA.
² Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
³ Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA.
⁴ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
⁵ Center for Radiological Research, Columbia University, New York, NY 10032, USA.
⁶ Science for Life Laboratory, Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
⁷ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA.
⁸ New England Biolabs, Ipswich, MA, USA.
⁹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital, Tubingen, Germany.
¹⁰ Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
¹¹ The Jackson Laboratories, Farmington, CT, USA.
¹² Department of Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹³ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
¹⁴ Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
¹⁵ Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Universities Space Research Association, Space Biosciences Division, NASA Ames Research Center, Mountain View, CA 94035, USA.
¹⁶ McAllister Heart Institute, Department of Pharmacology, and Department of Pathology and Lab Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁷ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
¹⁸ Department of Radiation Medicine, Georgetown University School of Medicine, Washington DC 20007, USA.
¹⁹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. Electronic address: chm2042@med.cornell.edu.
²⁰ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: afshin.beheshti@nasa.gov.

Abstract

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration and long-duration spaceflight. Previous studies have identified miRNAs that regulate rodent responses to spaceflight in low-Earth orbit, and we have confirmed the expression of these proposed spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions. Moreover, astronaut samples from the NASA Twins Study confirmed these expression signatures in miRNA sequencing, single-cell RNA sequencing (scRNA-seq), and single-cell assay for transposase accessible chromatin (scATAC-seq) data. Additionally, a subset of these miRNAs (miR-125, miR-16, and let-7a) was found to regulate vascular damage caused by simulated deep space radiation. To demonstrate the physiological relevance of key spaceflight-associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep-space-radiation-mediated damage in human 3D vascular constructs.

Keywords: NASA; Twins Study; antagomirs; miRNA-seq; microRNA; microgravity; scATAC-seq; scRNA-seq; space radiation; spaceflight.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Circulating MicroRNA / genetics*
Female
Gene Expression
Gene Expression Profiling / methods
Humans
Male
Mice
Mice, Inbred BALB C
MicroRNAs / genetics*
Middle Aged
Rats
Sequence Analysis, RNA / methods
Space Flight
Transcriptome / genetics
Weightlessness / adverse effects*
Weightlessness Simulation / methods

Substances

Circulating MicroRNA
MicroRNAs

Abstract

Publication types

MeSH terms

Substances

Grants and funding