Neurotrophins mediate human embryonic stem cell survival
Neurotrophins mediate human embryonic stem cell survival
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DOI：
10.1038/nbt1189
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发表时间：
2006-03-01
影响因子：
46.9
通讯作者：
Donovan, PJ
中科院分区：
文献类型：
--
作者：
Pyle, AD;Lock, LF;Donovan, PJ
人类胚胎干细胞（hES）作为多能群体的生长需要存活、增殖和自我更新信号之间的平衡。在这里，我们证明了hES细胞表达原肌球蛋白相关激酶（TRK）家族的受体，介导抗凋亡信号。我们发现三个TRK配体，脑源性神经营养因子，神经营养因子3和神经营养因子4，是hES细胞的存活因子。向hES细胞培养物中添加神经营养因子可使其克隆存活率提高36倍。在含有神经营养因子的培养基中维持的hES细胞培养物保持二倍体并保留完全发育潜能。在神经营养因子的存在下，hES细胞中的TRK受体被磷酸化; TRK受体抑制导致hES细胞凋亡。hES细胞中神经营养因子的存活活性由磷脂酰肌醇-3-激酶途径介导，而不是由丝裂原活化蛋白激酶途径介导。神经营养因子改善hES细胞存活，并可能促进其操作和高通量筛选的发展，以确定负责hES细胞分化的因素。
Growth of human embryonic stem (hES) cells as a pluripotent population requires a balance between survival, proliferation and self-renewal signals. Here we demonstrate that hES cells express receptors of the tropomyosin-related kinase (TRK) family, which mediate antiapoptotic signals. We show that three TRK ligands, brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4, are survival factors for hES cells. Addition of neurotrophins to hES cell cultures effects a 36-fold improvement in their clonal survival. hES cell cultures maintained in medium containing neurotrophins remain diploid and retain full developmental potency. In the presence of neurotrophins, TRK receptors in hES cells are phosphorylated; TRK receptor inhibition leads to hES cell apoptosis. The survival activity of neurotrophins in hES cells is mediated by the phosphatidylinositol-3-kinase pathway but not the mitogen-activated protein kinase pathway. Neurotrophins improve hES cell survival and may facilitate their manipulation and the development of high-throughput screens to identify factors responsible for hES cell differentiation.