Cited by 13Redox biology and oxidative stressPluripotent Stem Cells ResearchDown syndrome and intellectual disability research

Oxidative stress as a candidate mechanism for accelerated neuroectodermal differentiation due to trisomy 21

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Prutton, Kendra M., Marentette, John O., Leifheit, Brice A., Esquer, Hector, LaBarbera, Daniel V., Anderson, Colin C., Maclean, Kenneth N., Roede, James R.·2022·Free Radical Biology and Medicine

Abstract

The ubiquity of cognitive deficits and early onset Alzheimer's disease in Down syndrome (DS) has focused much DS iPSC-based research on neuron degeneration and regeneration. Despite reports of elevated oxidative stress in DS brains, few studies assess the impact of this oxidative burden on iPSC differentiation. Here, we evaluate cellular specific redox differences in DS and euploid iPSCs and neural progenitor cells (NPCs) during critical intermediate stages of differentiation. Despite successful generation of NPCs, our results indicate accelerated neuroectodermal differentiation of DS iPSCs compared to isogenic, euploid controls. Specifically, DS embryoid bodies (EBs) and neural rosettes prematurely develop with distinct morphological differences from controls. Additionally, we observed developmental stage-specific alterations in mitochondrial superoxide production and SOD1/2 abundance, coupled with modulations in thioredoxin, thioredoxin reductase, and peroxiredoxin isoforms. Disruption of intracellular redox state and its associated signaling has the potential to disrupt cellular differentiation and development in DS lending to DS-specific phenotypes.

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Crossref · 10.1016/j.freeradbiomed.2022.04.015

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  • Trisomy 21 iPSCs show accelerated neural differentiation that correlates with disruption of intracellular redox state and its associated signaling.

    “This study of trisomy 21 iPSCs reveals accelerated neural differentiation that correlates with disruption of intracellular redox state and its associated signaling.”

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Authors
Prutton, K. M., Marentette, J. O., Leifheit, B. A., Esquer, H., LaBarbera, D. V., Anderson, C. C., Maclean, K. N., & Roede, J. R.
Affiliations
University of Colorado Anschutz (US)
Corresponding author
Roede, James R.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2022-06
Volume
186
Pages
32-42
ISSN
0891-5849 (ISSN-L)
OpenAlex
W4229048962
Cited by
13
References
70
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 3
FWCI
0.82
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (acceptedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Environmental Health Sciences (R01ES027593, R25ES025476)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Keywords
Down syndrome, oxidative stress, neuroectodermal differentiation, induced pluripotent stem cells, neural progenitor cells, embryoid bodies, neural rosettes, mitochondrial superoxide, superoxide dismutase, thioredoxin, thioredoxin reductase, peroxiredoxin, redox state, iPSC differentiation
MeSH terms
Cell Differentiation, Cells, Cultured, Down Syndrome, Humans, Oxidative Stress, Induced Pluripotent Stem Cells

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