Neurotrophin receptor p75NTR characterizes human esophageal keratinocyte stem cells in vitro
Neurotrophin receptor p75NTR characterizes human esophageal keratinocyte stem cells in vitro
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DOI：
10.1038/sj.onc.1206525
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发表时间：
2003-06-26
期刊：
影响因子：
8
通讯作者：
Yasumoto, S
中科院分区：
文献类型：
--
作者：
Okumura, T;Shimada, Y;Yasumoto, S
我们在这里报告，人食管角质形成干细胞的特点是低亲和力神经营养因子受体p75（NTR）和差异表达的细胞粘附分子，β 1和β 4整合素的表达。候选干细胞可以通过基于这些细胞表面分子的不同表达水平的免疫细胞化学细胞分选从角质形成细胞中分离出作为次要细胞亚群。流式细胞术分析显示，这个小细胞亚群在体外保留了相对缓慢的循环表型。这些细胞表达低水平的外皮蛋白和细胞角蛋白13，表明p75（NTR）阳性细胞亚群是不成熟的相对于其他主要亚群共表达β 1整合素在较高的水平。p75（NTR）阳性细胞亚群是至关重要的实现长寿和最大的输出角质形成细胞包括所有可区分的亚群在体外。这一过程与p75（NTR）阳性细胞亚群的自我更新和自我扩增有关。这些发现强烈暗示p75（NTR）作为干细胞标志物，这将是有价值的前瞻性研究干细胞调控与不同的生物过程，包括再生上皮的肿瘤转化。
We report here that human esophageal keratinocyte stem cells are characterized by the expression of the low-affinity neurotrophin receptor p75(NTR) and differentially expressed cell adhesion molecules, the beta1 and beta4 integrins. The candidate stem cells could be fractionated from keratinocytes as a minor cell subset by means of immunocytochemical cell sorting based on the different levels of expression of these cell surface molecules. Flow cytometric analysis revealed that this minor cell subset retained a relatively slow-cycling phenotype in vitro. These cells expressed low levels of involucrin and cytokeratin 13, indicating that the p75(NTR)-positive cell subset is immature relative to the other predominant subpopulations coexpressing beta1 integrin at higher levels. The p75(NTR)-positive cell subset was crucial for achieving longevity and the greatest output of keratinocytes comprising all distinguishable subpopulations in vitro. This process was associated with self-renewal and self-amplification of the p75(NTR)-positive cell subset. These findings strongly implicate p75(NTR) as a stem cell marker, which will be valuable for prospectively investigating stem cell regulation in association with different biological processes including neoplastic transformation of regenerative epithelia.