Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell death.
Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell death.
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DOI：
10.1002/stem.107
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发表时间：
2009-08
期刊：
影响因子：
5.2
通讯作者：
Terskikh, Alexey V.
中科院分区：
文献类型：
--
作者：
Cimadamore, Flavio;Curchoe, Carol Lynn;Alderson, Nazilla;Scott, Fiona;Salvesen, Guy;Terskikh, Alexey V.
关键词：
Abundant cell death is observed when human embryonic stem cells (hESCs) undergo neuralization, a critical first step for future cell-based therapies addressing neurodegeneration. Using hESC neuralization as an in vitro model of human development, we demonstrated that the developing neuroepithelium acquires increased susceptibility to spontaneous cell death. We found that Poly(ADP-ribose) polymerase-1/Apoptosis Inducing Factor (PARP1/AIF)-mediated cell death (parthanatos) is a dominant mechanism responsible for cell loss during hESCs neuralization. The demise of neural progenitors cells (hNPCs), at least in part, is due to decreased endogenous antioxidant defenses and enhanced reactive oxygen species (ROS) leakage from mitochondria fuelled by non-physiological culture conditions. Under such conditions, PARP1 over-activation triggered cell death through the mitochondrial-nuclear translocation of AIF. Blocking PARP1 activity with shRNAi or nicotinamide dramatically enhanced hESC neuralization, providing optimal survival of the developing neuroepithelium. Because nicotinamide is a physiological metabolite, our results raise the possibility that neural stem/progenitor cell survival in vivo requires a metabolic niche. We argue that small natural metabolites provide a powerful physiological tool to optimize hESC differentiation compatible with requirements of regenerative medicine.
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影响因子：
21.3
作者：
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通讯作者：
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DOI：
10.1016/s0034-5687(01)00306-1
发表时间：
2001-11-15
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Maynard, KI
DOI：
10.1073/pnas.0606526103
发表时间：
2006-11-28
影响因子：
11.1
作者：
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通讯作者：
Dawson, Ted M.