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@article{1126893,
author = {Vinarský, Vladimír and Křivánek, Jan and Rankel, Liina and Nahacka, Zuzana and Bárta, Tomáš and Jaroš, Josef and Andera, Jaroslav and Hampl, Aleš},
article_location = {New York},
article_number = {22},
doi = {http://dx.doi.org/10.1089/scd.2013.0057},
keywords = {TUMOR-NECROSIS-FACTOR; EXTRINSIC APOPTOSIS; MEDIATED APOPTOSIS; SELF-RENEWAL; DNA-DAMAGE; DEATH; CASPASE-8; SURVIVAL; STRESS; ACTIVATION},
language = {eng},
issn = {1547-3287},
journal = {Stem Cells and Development},
title = {Human Embryonic and Induced Pluripotent Stem Cells Express TRAIL Receptors and Can Be Sensitized to TRAIL-Induced Apoptosis},
volume = {22},
year = {2013}
}
TY - JOUR
ID - 1126893
AU - Vinarský, Vladimír - Křivánek, Jan - Rankel, Liina - Nahacka, Zuzana - Bárta, Tomáš - Jaroš, Josef - Andera, Jaroslav - Hampl, Aleš
PY - 2013
TI - Human Embryonic and Induced Pluripotent Stem Cells Express TRAIL Receptors and Can Be Sensitized to TRAIL-Induced Apoptosis
JF - Stem Cells and Development
VL - 22
IS - 22
SP - 2964-2974
EP - 2964-2974
PB - MARY ANN LIEBERT INC
SN - 15473287
KW - TUMOR-NECROSIS-FACTOR
KW - EXTRINSIC APOPTOSIS
KW - MEDIATED APOPTOSIS
KW - SELF-RENEWAL
KW - DNA-DAMAGE
KW - DEATH
KW - CASPASE-8
KW - SURVIVAL
KW - STRESS
KW - ACTIVATION
N2 - Death ligands and their tumor necrosis factor receptor (TNFR) family receptors are the best-characterized and most efficient inducers of apoptotic signaling in somatic cells. In this study, we analyzed whether these prototypic activators of apoptosis are also expressed and able to be activated in human pluripotent stem cells. We examined human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC) and found that both cell types express primarily TNF-related apoptosis-inducing ligand (TRAIL) receptors and TNFR1, but very low levels of Fas/CD95. We also found that although hESC and hiPSC contain all the proteins required for efficient induction and progression of extrinsic apoptotic signaling, they are resistant to TRAIL-induced apoptosis. However, both hESC and hiPSC can be sensitized to TRAIL-induced apoptosis by co-treatment with protein synthesis inhibitors such as the anti-leukemia drug homoharringtonine (HHT). HHT treatment led to suppression of cellular FLICE inhibitory protein (cFLIP) and Mcl-1 expression and, in combination with TRAIL, enhanced processing of caspase-8 and full activation of caspase-3. cFLIP likely represents an important regulatory node, as its shRNA-mediated down-regulation significantly sensitized hESC to TRAIL-induced apoptosis. Thus, we provide the first evidence that, irrespective of their origin, human pluripotent stem cells express canonical components of the extrinsic apoptotic system and on stress can activate death receptor-mediated apoptosis.
ER -
VINARSKÝ, Vladimír, Jan KŘIVÁNEK, Liina RANKEL, Zuzana NAHACKA, Tomáš BÁRTA, Josef JAROŠ, Jaroslav ANDERA a Aleš HAMPL. Human Embryonic and Induced Pluripotent Stem Cells Express TRAIL Receptors and Can Be Sensitized to TRAIL-Induced Apoptosis. Online. \textit{Stem Cells and Development}. New York: MARY ANN LIEBERT INC, 2013, roč.~22, č.~22, s.~2964-2974. ISSN~1547-3287. Dostupné z: https://dx.doi.org/10.1089/scd.2013.0057. [citováno 2024-04-24]
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