Cell stem cell · 2025
Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Pham Jessica, Isquith Jane, Balaian Larisa, Nandi Shuvro P, Engstrom Claire, Mack Karla, van der Werf Inge, Chang Patrick, Stoudemire Jana, Ladel Luisa, Klacking Emma, Ruiz Antonio, Chilin-Fuentes Daisy, Sneifer Jenna, Mays David, Gamble Paul, Giza Shelby, Janowitz Jiya, Nienaber Trevor, Mishra Tejaswini, Khachatrian Anna A, Molina Elsa, Snyder Michael P, Morris Sheldon R, Clements Twyman, Muotri Alysson R, Whisenant Thomas, Alexandrov Ludmil B, Jamieson Catriona H M
Аннотация
Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team developed bone marrow niche nanobioreactors with lentiviral bicistronic fluorescent, ubiquitination-based cell-cycle indicator (FUCCI2BL) reporter for real-time HSPC tracking in artificial intelligence (AI)-driven CubeLabs. In month-long International Space Station (ISS) missions (SpX-24, SpX-25, SpX-26, and SpX-27) compared with ground controls, FUCCI2BL reporter, whole-genome and transcriptome sequencing, and cytokine arrays demonstrated cell-cycle, inflammatory cytokine, mitochondrial gene, human repetitive element, and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) deregulation together with clonal hematopoietic mutations. Furthermore, HSPC functionally organized multi-omics aging (HSPC-FOMA) analyses revealed reduced telomere maintenance, adenosine deaminase acting on RNA1 (ADAR1) p150 self-renewal gene expression, and replating capacity indicative of space-associated HSPC aging that may limit long-duration spaceflight.