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. 2025 Sep 4;32(9):1403-1420.e8.
doi: 10.1016/j.stem.2025.07.013.

Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging

Jessica Pham  1 , Jane Isquith  1 , Larisa Balaian  1 , Shuvro P Nandi  2 , Claire Engstrom  1 , Karla Mack  1 , Inge van der Werf  1 , Patrick Chang  1 , Jana Stoudemire  1 , Luisa Ladel  1 , Emma Klacking  1 , Antonio Ruiz  1 , Daisy Chilin-Fuentes  3 , Jenna Sneifer  1 , David Mays  4 , Paul Gamble  4 , Shelby Giza  4 , Jiya Janowitz  4 , Trevor Nienaber  4 , Tejaswini Mishra  5 , Anna A Khachatrian  6 , Elsa Molina  7 , Michael P Snyder  5 , Sheldon R Morris  1 , Twyman Clements  4 , Alysson R Muotri  1 , Thomas Whisenant  3 , Ludmil B Alexandrov  8 , Catriona H M Jamieson  9
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Free article

Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging

Jessica Pham et al. Cell Stem Cell. .
Free article

Abstract

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.

Keywords: ADAR1; APOBEC3; aging; cell cycle; clonal hematopoiesis; dark genome; hematopoietic stem and progenitor cells; low-earth orbit; nanobioreactor; repetitive elements.

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Conflict of interest statement

Declaration of interests C.H.M.J. is a co-founder of Impact Biomedicines and Aspera Biomedicines. C.H.M.J. has received royalties from Forty Seven Inc. S.R.M. is a co-founder of Aspera Biomedicines. K.M. is an employee of Aspera Biomedicines. M.P.S. is a co-founder of Personalis, SensOmics, Qbio@qbioinc, January AI, Filtricine, Mirvie, Protos, Protometrix (now part of Thermo Fisher), and Affomix (now part of Illumina). A.R.M. is a co-founder and has an equity interest in TISMOO. L.B.A. is a co-founder of IO9. L.L., J.P., L.B., A.R., E.K., T.W., and C.H.M.J. are named on patents related to this work.

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