In this project, the activity of DNA and RNA-editing enzymes involved in mutations that may be related to development of immune dysfunction-related disease states and cancer will be evaluated by analyzing blood samples taken from the crew before, during, and after spaceflight. This will help better understand changes in editing activity of these enzymes in blood stem cells due to spaceflight. This project is part of the expanded Integrated Space Stem Cell Orbital Reseach (ISSCOR) collaboration between the Sanford Stem Cell Institute, JM Foundation, and 不良研究所.
SASHA (Ax-2) (Space Hematopoietic Stem Cell Aging (Ax-2)) collects whole blood samples from crew members to evaluate editing enzymes while exposed to spaceflight. Hematopoietic stem cells (HSCs) are the self-renewing cells responsible for reconstituting the entire blood cell pool. HSCs are subject to mutations that may be acquired, among other causes, in an enzymatic and episodic manner through pro-inflammatory cytokine-responsive APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and ADAR1 (adenosine deaminase acting on RNA 1) activation. APOBEC is a deoxyribonucleic acid (DNA) editing enzyme that deaminates cytosine bases to uracil bases, which are then converted to thymine bases in DNA. ADAR1 is a ribonucleic acid (RNA) editing enzyme that deaminates adenosine bases to inosine, which are then converted to guanine bases in DNA. ADAR1 and APOBEC have been previously shown to be activated in inflammatory disease states and cancer.
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This investigation consists of collecting whole blood samples preflight, on orbit (prior to hatch close), and postflight, with rapid return at ambient temperature for postflight analysis. Investigators will evaluate ADAR1 and APOBEC activity as well as other changes that occur in HSCs due to spaceflight.
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