Function of ID1 protein in human cord blood-derived neural stem-like cells
Function of ID1 protein in human cord blood-derived neural stem-like cells
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DOI：
10.1002/jnr.20994
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发表时间：
2006-10-01
影响因子：
4.2
通讯作者：
Domanska-Janik, K.
中科院分区：
文献类型：
--
作者：
Jurga, M.;Buzanska, L.;Domanska-Janik, K.
研究了ID1蛋白碱性螺旋-环-螺旋（bHLH）转录因子的显性负调控因子对人脐带血神经干细胞样细胞系（HUCB-NSC）生长和分化的影响。这种未转化的中胚层起源系含有高水平的ID1蛋白，其细胞间分布反映了HUCB-NSC分化状态。而在无血清（SF）培养中，细胞保持未分化和自我更新，ID1蛋白虽然高表达，但没有到达细胞核，主要定位在细胞质中。在低血清浓度（LS）培养的部分承诺（引物）HUCB-NSC的长期扩增培养中，ID1蛋白向细胞核转移。进一步的神经元分化，无论是在血清存在下自发的，还是在神经形态因子（dBcAMP， RA）的诱导下，导致ID1 mRNA和蛋白几乎完全消失。因此，过表达ID1基因的HUCB-NSC转染物的分化受到明显抑制。值得注意的是，ID1过表达后只影响神经元的发育，而不影响胶质细胞的发育。在髓母细胞瘤来源的人nsc样细胞系（DEV）中观察到类似的ID1转染的功能获得效应，该细胞系构成性地缺乏ID1的表达。因此，我们对HUCB-NSC的研究结果进一步证实了其神经特异性行为和ID1蛋白作为神经干细胞分化的一个强有力的负调节因子的关键作用，并指出这种蛋白在细胞质和核细胞间的分布可能是分化信号转导的最重要步骤之一。(c) 2006 Wiley-Liss, Inc。
The effect of dominant-negative regulator of basic helix-loop-helix (bHLH) transcription factors, an ID1 protein, on growth and differentiation of neural stem-like cell line derived from human umbilical cord blood (HUCB-NSC) was investigated. This nontransformed, mesodermal germ layer-originated line contains high levels of ID1 protein, whose intercellular distribution reflects HUCB-NSC differentiation status. Whereas cells remained undifferentiated and self-renewing in serum-free (SF) cultures, ID1 protein, although highly expressed, did not attain cell nuclei and was localized mainly in cytoplasm. In long-term-expanded cultures of partially committed (primed) HUCB-NSC grown in a low serum concentration (LS cultures) ID1 protein became translocated toward cell nuclei. Further neuronal differentiation of the cells, either spontaneous in the presence of serum or induced by neuromorphogens (dBcAMP, RA), resulted in almost complete depletion of ID1 mRNA and protein. Accordingly, HUCB-NSC transfectants overexpressing the ID1 gene were significantly inhibited in their differentiation. Notably, only neuronal and not glial development was affected after ID1 overexpression. A similar gain-of-function effect of ID1 transfection was observed in human NSC-like line (DEV) of medullobastoma origin, which is constitutively devoid of ID1 expression. Thus, our results on HUCB-NSC confirm further its neural-specific behavior and the crucial role of ID1 protein as a potent negative regulator of neural stem cell differentiation, pointing out that this protein distribution between cytoplasmic and nuclear cell compartments can be one of the most important steps in differentiation signal transduction. (c) 2006 Wiley-Liss, Inc.