TY - JOUR
T1 - Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging
AU - Pham, Jessica
AU - Isquith, Jane
AU - Balaian, Larisa
AU - Nandi, Shuvro P.
AU - Engstrom, Claire
AU - Mack, Karla
AU - van der Werf, Inge
AU - Chang, Patrick
AU - Stoudemire, Jana
AU - Ladel, Luisa
AU - Klacking, Emma
AU - Ruiz, Antonio
AU - Chilin-Fuentes, Daisy
AU - Sneifer, Jenna
AU - Mays, David
AU - Gamble, Paul
AU - Giza, Shelby
AU - Janowitz, Jiya
AU - Nienaber, Trevor
AU - Mishra, Tejaswini
AU - Khachatrian, Anna A.
AU - Molina, Elsa
AU - Snyder, Michael P.
AU - Morris, Sheldon R.
AU - Clements, Twyman
AU - Muotri, Alysson R.
AU - Whisenant, Thomas
AU - Alexandrov, Ludmil B.
AU - Jamieson, Catriona H.M.
N1 - Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2025/9/4
Y1 - 2025/9/4
N2 - 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.
AB - 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.
KW - ADAR1
KW - APOBEC3
KW - aging
KW - cell cycle
KW - clonal hematopoiesis
KW - dark genome
KW - hematopoietic stem and progenitor cells
KW - low-earth orbit
KW - nanobioreactor
KW - repetitive elements
KW - Humans
KW - Space Flight
KW - Hematopoietic Stem Cells/cytology
KW - Cellular Senescence
UR - https://www.scopus.com/pages/publications/105014547160
UR - https://www.mendeley.com/catalogue/e0f5d541-ed09-3d93-857f-007fd22a2836/
U2 - 10.1016/j.stem.2025.07.013
DO - 10.1016/j.stem.2025.07.013
M3 - Article
C2 - 40912236
AN - SCOPUS:105014547160
SN - 1934-5909
VL - 32
SP - 1403-1420.e8
JO - Cell stem cell
JF - Cell stem cell
IS - 9
ER -