Maria MorenoVillanueva 12 Stephanie Krieger 3 Ye Zhang 4 Brian Crucian 1 Honglu Wu 1 1 NASA Johnson Space Center Houston Texas 2 University of Konstanz Konstanz Germany ID: 1045907
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1. TRANSCRIPTOMIC CHANGES IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF INTERNATIONAL SPACE STATION CREWMEMBERS Maria Moreno-Villanueva1,2, Stephanie Krieger3, Ye Zhang4, Brian Crucian1, Honglu Wu1 1NASA Johnson Space Center, Houston, Texas, 2University of Konstanz, Konstanz, Germany, 3KBR, Houston, Texas, 4NASA Kennedy Space Center, Cape Canaveral, FloridaCOSPAR, Athens, July, 2022
2. Blood collection schedule (Functional Immune)Blood drawn in flight was transported to JSC at ambient temperature.For crewmembers, the R0 samples were drawn immediately after returning to JSC, or in the case of international astronauts, after returning to DLR .Blood samples drawn from crewmembers and from ground matching subjects at JSC were aged.Data from 8 crewmembers are discussed here.
3. Number of differentially expressed genesRNA was isolated from peripheral blood mononuclear cells (PBMC).Transcriptomics analysis was performed using RNA-seq.Differentially expressed genes were determined by performing contrast analysis, using all time points of the ground control subjects combined as a control.The fold change threshold is 1.5 and the FDR < 0.05.
4. Selected differentially expressed genesCDKN1A (p21) was downregulated in space.Several NFkB and NFkB inhibitor genes were upregulated in space.
5. Upstream regulators (Ingenuity Pathway Analysis, IPA)Upstream regulators were determined using z>2.0 and p<0.05 as thresholds.No significant upstream regulators were identified for other pre- and post-flight time points.
6. Upstream regulators (Continued)Most of the regulation relationships were activation at R0.NFkB genes (NFKB1, REL and RELA) were identified as upstream regulators.Does the data indicate adaptation at LF?
7. Pathway Analysis (IPA)Among the canonical pathways are cardiac hypertrophy, osteoarthritis and neuroinflammation (Z>2, p<0.05). These pathways are activated more at LF.
8. Chronic activation of NFkB in spaceChronic activation of NFkB may be related to chronic inflammation and other causes.Chronic activation of NFkB in space can be associated with several health risks (Zhang et al. Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences. Int J Mol Sci 2017).
9. Alterations of Immune Related Genes Proteins in plasma were measured in Functional Immune project.A comparison between plasma cytokines and gene expression in PBMC will be made on crewmembers from the same study.A preliminary comparison shows similarities between sample types was found for some of the cytokines such as IL-1B and GM-CSF.Gene expression change
10. SenescenceSeveral senescence related genes such as CDKN1A (p21), p53 and TGFb were downregulated in space.Can senescence provide an explanation for telomere lengthening in space?Immune dysfunctionOsteoarthritisNeuroinflammation Cardiac hypertrophy Association with other risksmicroRNA data is being analyzedPotential implications of the transcriptomics data
11. CONCLUSIONSResults of the preliminary analysis indicate that most of the gene expression changes occurred at MF, LF and R+0, with most of these expression levels returning to baseline by R+30. A number of cell cycle related genes such as p21 and VEGF were downregulated in space.Our data suggests chronic activation of the NFkB pathway during flight.There appears to be an adaptation to the space environment at LF time point.Network analysis of the RNA data suggests a spaceflight effect on pathways not only in the immune system, but also on others involving neuroinflammation and oxidative stress.
12. ACKNOWLEDGEMENTNASA JSCGeorge MakedonasUniversity of WisconsinMark BerresSandra Splinter BonDurant Uniformed Services University Brian C. SchaeferThis work is supported by the NASA Human Research Program.