Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors.
Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors.
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DOI：
10.1186/1471-2202-6-59
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发表时间：
2005-09-13
期刊：
影响因子：
2.4
通讯作者：
Miranda RC
中科院分区：
文献类型：
--
作者：
Santillano DR;Kumar LS;Prock TL;Camarillo C;Tingling JD;Miranda RC
胎儿皮质神经上皮是一个镶嵌的不同祖细胞群体，阐述了不同的细胞命运。乙醇诱导细胞凋亡并干扰分化中神经元的存活。然而，我们对乙醇对神经元祖细胞的影响知之甚少。因此，我们将胎鼠大脑皮层的神经球培养物暴露于不同浓度的乙醇中，以研究乙醇对干细胞命运的影响。乙醇促进细胞周期进程，增加神经球数量和神经球大小的多样性，而不诱导凋亡。与对照组不同，暴露于乙醇的分离的皮质祖细胞表现出不对称细胞分裂的形态学证据，来自乙醇预处理的神经球的细胞表现出增殖能力下降。乙醇显著减少表达干细胞标志物CD 117、CD 133、Sca-1和ABCG 2的细胞数量，而不降低巢蛋白表达。此外，乙醇诱导的神经球增殖并不伴随着端粒酶活性的相应增加。最后，来自乙醇预处理的神经球的细胞表现出响应于视黄酸的分化降低。干细胞数量的减少沿着短暂的乙醇驱动的细胞增殖的增加，表明乙醇促进干细胞向母细胞的成熟，最终耗尽神经上皮细胞的储备增殖能力。然而，缺乏伴随的端粒酶活性的变化表明，神经上皮细胞的成熟伴随着基因组不稳定性的可能性增加。最后，从乙醇预处理的干细胞耗尽的神经球中出现的细胞表型对额外的分化刺激是难治的，这表明乙醇暴露消融或延迟随后的神经元分化。
The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.
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DOI：
10.1006/bbrc.2001.5271
发表时间：
2001-07-27
影响因子：
3.1
作者：
Corbeil, D;Fargeas, CA;Huttner, WB
通讯作者：
Huttner, WB
影响因子：
20.3
作者：
Dai, MS;Mantel, CR;Lu, L
通讯作者：
Lu, L
影响因子：
4
作者：
Epting, CL;López, JE;Bernstein, HS
通讯作者：
Bernstein, HS
影响因子：
4.3
作者：
Chen, HC;Frissora, F;Muthusamy, N
通讯作者：
Muthusamy, N
影响因子：
4.2
作者：
GOTTESFELD, Z;MORGAN, B;PEREZPOLO, JR
通讯作者：
PEREZPOLO, JR