Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation.
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.
Buck Institute for Research on Aging, Novato, CA 94945, USA.
Ying
Y
Zou
Ningzhe
N
Zhang
Lisa M
LM
Ellerby
Albert R
AR
Davalos
Xianmin
X
Zeng
Judith
J
Campisi
Pierre-Yves
PY
Desprez
D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000528:radiation effects*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000528:radiation effects; D011836:Radiation Tolerance
D015415:Biomarkers