Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation
Open accessAbstract
Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety of neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5-7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.
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DNA damage-induced cellular senescence can occur together with cell differentiation.
“Thus, DNA damage-induced cellular senescence can coincide with cell differentiation128,129.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [129]
In response to various stressors such as hydrogen peroxide and ionizing radiation, astrocytes become senescent.
“Indeed, in response to various stressors such as hydrogen peroxide [9] and ionizing radiation [173], astrocytes become senescent.”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [173]
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- Authors
- Zou, Y., Zhang, N., Ellerby, L. M., Davalos, A. R., Zeng, X., Campisi, J., & Desprez, P.-Y.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Desprez, Pierre-Yves
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 426
- Issue
- 1
- Pages
- 100-105
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC3498829
- OpenAlex
- W1966056603
- Cited by
- 41
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AG09909, AG017242, CA126540)
- Department of Defense (BC096367, CL1-00501)
- California Institute for Regenerative Medicine
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- human embryonic stem cells, ionizing radiation, neuronal stem cells, neurons, genotoxic stress response, cellular senescence, senescence-associated secretory phenotype, radiation-induced cell death, oncogenic transformation
- MeSH terms
- Astrocytes, Cell Differentiation, Cell Survival, Cells, Cultured, DNA Damage, Humans, Neurons, Radiation Tolerance, Biomarkers, Cellular Senescence, Embryonic Stem Cells, Neural Stem Cells
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